The effects of eicosapentaenoic acid ethyl ester (EPA-E) on arterial thrombosis in rabbits and vascular lesions in rats

The effects of highly purified ethyl ester of eicosapentaenoic acid (EPA-E) on ellagic acid-induced thrombus formation in the stenosed femoral artery in rabbits and on the progression of laurate-induced vascular lesions in rats were examined. (1) EPA-E in single administration significantly prevented the thrombus formation induced by ellagic acid in the stenosed femoral artery of rabbits. (2) EPA-E restored the hypercoagulation activity at 5 min and 3 hr after the ellagic acid injection. Platelet aggregability induced by arachidonic acid decreased at 5 min and 3 hr after the ellagic acid injection; EPA-E had little effect on this change. EPA-E showed almost no effect on fibrinolytic activity, blood viscosity and filterability of washed red blood cells after the ellagic acid injection. (3) Moreover, EPA-E in daily administrations showed a significant preventative effect against the laurate-induced vascular lesions in rats. The efficacy of EPA-E on arterial thrombosis and vascular lesions observed in this study suggests that EPA-E is a candidate for the treatment of peripheral circulatory disturbance.     

Evaluation of initial hepatic allograft function with changes of free plasma amino acids in canine orthotopic liver transplantation

We investigated the correlation between amino acid level and hepatic graft function. Plasma amino acid levels were measured at three time periods during canine orthotopic liver transplantation. During the anhepatic phase, plasma amino acid levels rose except for tryptophan. Cystine and alanine (Ala) increased significantly to 210 +/- 28% (n = 20, mean +/- SEM) and 203 +/- 11% from preoperative values (100%), respectively. In animals successfully surviving without hepatic insufficiency after transplantation of fresh livers (n = 7), plasma amino acid levels were restored to preoperative values within 3 hr following reperfusion. On the other hand, in animals that died from hepatic insufficiency within 5 days after grafting of warm ischemically damaged livers (n = 8), plasma amino acids, especially Ala, phenylalanine, total free plasma amino acids, and aromatic amino acids progressively increased to 216 +/- 25, 274 +/- 36, 152 +/- 15, and 152 +/- 15% at 3 hr after reperfusion. These were significantly higher compared to those of the group of animals transplanted with fresh livers (P less than 0.01-0.05). Furthermore, higher values were found in those dogs transplanted with warm ischemically damaged livers surviving for shorter periods. Also in dogs that died from hepatic insufficiency within 8 hr after grafting of livers preserved for 24 hr (n = 5), amino acid levels were at high values at 3 hr. These results suggest that in animals having good graft function, plasma amino acid levels are restored to preoperative values by 3 hr after reperfusion. In other cases, primary nonfunction should be strongly suspected after liver transplantation.     

An experimental evaluation of the order of revascularization after interrupting hepatic afferent blood flow

The purpose of this study was to investigate the influence of the order of revascularization on hepatic metabolic function after interruption of hepatic afferent blood flow to reconstruct the portal vein and the hepatic artery. Hepatic ischemia was induced in male rabbits by clamping the afferent hepatic blood supply. In the cases in which portal blood flow was released after 15 min of hepatic ischemia and hepatic arterial blood flow was released 15 min later, hepatic metabolic function, which was assessed by arterial ketone body ratio, plasma lactate, and hepatic energy charge levels, recovered immediately. When hepatic arterial blood flow was released in the reverse order, the recovery of hepatic function was delayed. In the cases in which portal and hepatic arterial blood flow were released simultaneously after 30 min of hepatic ischemia, hepatic function did not recover even 180 min after reperfusion. In contrast, the venous bypass was established during portal clamping, restoration of hepatic function was accelerated, and there was no significant difference in restoration between the methods of releasing portal blood flow first or releasing hepatic arterial blood flow first. In the method of simultaneous releasing, however, it was most delayed, probably due to the prolonged ischemic time. These results suggest that releasing first the portal or hepatic arterial blood flow with the establishment of venous bypass during the portal clamping would be the best order of revascularization for hepatic function when reconstructing the portal vein and the hepatic artery.     

Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation

Learning is accompanied by modulation of postsynaptic signal transduction pathways in neurons. Although the neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) has been implicated in cognitive disorders, its role in learning has been obscured by the perinatal lethality of constitutive knockout mice. Here we report that conditional knockout of Cdk5 in the adult mouse brain improved performance in spatial learning tasks and enhanced hippocampal long-term potentiation and NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents. Enhanced synaptic plasticity in Cdk5 knockout mice was attributed to reduced NR2B degradation, which caused elevations in total, surface and synaptic NR2B subunit levels and current through NR2B-containing NMDARs. Cdk5 facilitated the degradation of NR2B by directly interacting with both it and its protease, calpain. These findings reveal a previously unknown mechanism by which Cdk5 facilitates calpain-mediated proteolysis of NR2B and may control synaptic plasticity and learning.     

Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice

Once their safety is confirmed, human-induced pluripotent stem cells (hiPSCs), which do not entail ethical concerns, may become a preferred cell source for regenerative medicine. Here, we investigated the therapeutic potential of transplanting hiPSC-derived neurospheres (hiPSC-NSs) into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) mice to treat spinal cord injury (SCI). For this, we used a hiPSC clone (201B7), established by transducing four reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc) into adult human fibroblasts. Grafted hiPSC-NSs survived, migrated, and differentiated into the three major neural lineages (neurons, astrocytes, and oligodendrocytes) within the injured spinal cord. They showed both cell-autonomous and noncell-autonomous (trophic) effects, including synapse formation between hiPSC-NS-derived neurons and host mouse neurons, expression of neurotrophic factors, angiogenesis, axonal regrowth, and increased amounts of myelin in the injured area. These positive effects resulted in significantly better functional recovery compared with vehicle-treated control animals, and the recovery persisted through the end of the observation period, 112 d post-SCI. No tumor formation was observed in the hiPSC-NS-grafted mice. These findings suggest that hiPSCs give rise to neural stem/progenitor cells that support improved function post-SCI and are a promising cell source for its treatment.     

A case of perforated multiple gastric duplication cysts with five-layered appearance on ultrasonography

A case of perforated multiple gastric duplication cysts is presented. One of the gastric duplication cysts without perforation was seen on ultrasonography (US) with the following specific findings of gastric duplication cysts: a five-layered appearance, fold-like structures in the wall, and blood supply from the gastroepiploic artery. Other cysts with perforation presented with irregular and thin walls with a lack of the “double-wall sign” on US. These characteristic findings may be specific to perforated multiple gastric duplication cysts.     

Spontaneous disappearance of a middle fossa arachnoid cyst associated with subdural hematoma

The case of a 7-year-old boy with a middle fossa arachnoid cyst that spontaneously disappeared is presented. Computed tomography (CT) scan revealed an arachnoid cyst in the right middle fossa with a thin subdural hematoma on the same side. As the subdural hematoma spontaneously resolved, the cyst became smaller and finally disappeared without surgical intervention after 18 months on the follow-up CT scans. Possible mechanisms of the spontaneous disappearance of an arachnoid cyst are discussed.     

Repeat liver resection for hepatocellular carcinoma

BACKGROUND: Although hepatectomy has been accepted as a therapeutic option for the primary tumor of hepatocellular carcinoma (HCC), what role the second liver resection will play in the clinical care of patients with intrahepatic recurrence of HCC after the initial resection has not been well evaluated. STUDY DESIGN: In a retrospective review of the 6-year period between January 1991 and December 1996, records were examined of 94 patients who underwent curative liver resection for HCC. Of these, 57 patients had isolated recurrent disease to the liver; 12 of the 57 patients underwent repeat surgical resection and 45 patients received nonsurgical ablative therapy. Clinical data for these patients were reviewed for operative morbidity and mortality, survival, disease-free survival, and pattern of failure. RESULTS: There were no perioperative deaths during repeat liver resections for recurrent HCC. Operative morbidity in the second resection was comparable to the initial resection. The disease-free survival rate after the second hepatectomy was 31% at 2 years, significantly lower than that after initial hepatectomy (62%) (p = 0.009). The overall survival rate after the second hepatectomy was 90% at 2 years, in contrast to 70% after nonsurgical ablative treatment for recurrent HCC (p = 0.253). CONCLUSIONS: Although the second liver resection for recurrent HCC can be performed safely and may improve survival, the disease-free survival rate after such resection therapy is low. This likelihood of further recurrences encourages studies for the selection of patients who may benefit from repeat liver resection.     

Laparoscopic modified Thal fundoplication for gastroesophageal reflux in a patient with severe scoliosis and sliding esophageal hiatal hernia

A 14-year-old girl with severe scoliosis and sliding esophageal hiatal hernia underwent laparoscopic fundoplication for gastroesophageal reflux. Of various fundoplication procedures, anterior partial fundoplication (Thal fundoplication) was performed because it is effective, with less postoperative gas bloat syndrome. Laparoscopic fundoplication in severely scoliotic children could allow improved operative visibility and easier access to the hiatus in comparison with the open approach. In our “modified anterior partial fundoplication,” the sutures between the crura and the esophagus and the sutures on the left of esophageal wall with the fundus of the stomach could be exactly performed by laparoscopic surgical technique. The wrapping of the esophagus in fundoplication was done over the ventral 180° to 270°. Six months postoperatively, the patient did not develop gas bloat syndrome, distal esophageal obstruction from fundoplication, and delayed gastric emptying. Modified anterior partial fundoplication achieves effective control of reflux symptoms.