The therapeutic window of hypothermic neuroprotection in experimental ischemic neuropathy: protection in ischemic phase and potential deterioration in later reperfusion phase

Hypothermia will neuroprotect peripheral nerve from ischemia-reperfusion (IR) injury, but the therapeutic window of hypothermic neuroprotection has not been defined. Unilateral IR injury was produced by the ligation and release of nooses tied around supplying arteries to the right sciatic-tibial nerve of the rat. Using this model, 114 rats were divided into 12 groups according to the delay (0, 1, 3, and 4 h) and the depth of hypothermia (28, 32, and 35 degrees C). All rats were subjected to 3 h ischemia and 7 days reperfusion followed by behavioral, electrophysiological, and pathological evaluations. We demonstrated significant hypothermic neuroprotection with both deep (28 degrees C) and mild (32 degrees C) hypothermia initiated during ischemia (0 and 1 h delay), but not hypothermia initiated during reperfusion (3 and 4 h delay) in both behavioral and electrophysiological evaluations. In addition, the pathologically significant differences were observed between deep hypothermia (28 degrees C) and normothermia (35 degrees C) initiated during ischemia. We conclude that the therapeutic window of hypothermic neuroprotection is optimal during the intraischemic period and that mild and deep hypothermia provide neuroprotection. Prolonged delay of hypothermic treatment results in worsening of IR injury.     

Chemotherapy for the patients with esophageal cancer

The combination of cisplatin and continuous-infusion 5-fluorouracil is the standard regimen for the treatment of both squamous cell carcinoma and adenocarcinoma. Paclitaxel has shown favorable results as a single agent or in combination with cisplatin. The efficacy of neoadjuvant chemotherapy in terms of survival benefit remains controversial despite large-scale, randomized, controlled trials comparing it with surgery alone. The disease-free survival benefit of postoperative adjuvant chemotherapy was recognized in a Japan Clinical Oncology Group randomized controlled trial in comparison with surgery alone.     

Oxidative Coupling Copolymerization of 4‐Methyltriphenylamine with Arenes

A novel synthetic method for the preparation of high‐molecular‐weight conjugated polymers is presented. It consists of the oxidation copolymerization of different arenes with triphenylamine. The structure of the copolymers was characterized by ¹H and ¹³C NMR spectra. The copolymers have good solubility in common organic solvents and are thermally stable. Photoluminescence (PL) spectra (see Figure) showed that the color of emission depends on the type of arene units in the copolymer chain. Cyclic voltammetry (CV) measurements revealed electrochemical activity of the copolymers.

PL spectra of the copolymers.     

A neo-esophagus reconstructed by cultured human esophageal epithelial cells, smooth muscle cells, fibroblasts, and collagen

The scientists involved in this study attempted to develop an artificial esophagus constructed of autologous cells grown by cell culture methods on an extracellular matrix. An artificial esophagus consisting of human esophageal epithelial cells, dermal fibroblasts, and smooth muscle cells isolated from the aortic media, was attempted. The purpose of this study was to examine whether smooth muscle cells could be used in the transforming matrix. Human fibroblasts were embedded in Type I collagen superimposed on the collagen layer of smooth muscle cells. Next, human esophageal epithelial cells were cultured on the collagen layer of the fibroblasts. The resulting collagen sheets were cultured in vitro for 1 week, then transplanted on the latissimus dorsi muscles of athymic rats. The sheets were examined histologically at 1 and 2 weeks using hematoxylin eosin and immunologic stain methods (antiactin antibody). At the end of 2 weeks after transplantation, on microscopic observation of the collagen sheets, it appeared that the epithelial layer, the submucosal tissue layer, and the proper muscle layer had been reconstructed. Additionally, the authors successfully isolated smooth muscle cells from the media of the left gastric artery as a surgical specimen by explant cell culture. The ability to transform collagen sheets consisting of esophageal epithelial cells, fibroblasts, and smooth muscle cells from a surgical specimen into a luminal structure may enable clinical application of the artificial esophagus.     

Effects of baicalein isolated from roots of Scutellaria baicalensis Georgi on interleukin 1β- and tumour necrosis factor α-induced tissue-type plasminogen activator and plasminogen activator inhibitor-1 production in cultured human umbilical vein endothelial cells

The effects were examined of baicalein on tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) production stimulated by interleukin-1α (IL-1β) and tumour necrosis factor-α (TNF-α) in cultured human vein umbilical endothelial cells (HUVECs). IL-1β and TNF-α increased PAI-1 production, but they decreased t-PA production. Baicalein isolated from the roots of Scutellaria baicalensis Georgi, inhibited the PAI-1 production stimulated by IL-1β and TNF-α, but it had no effect on the t-PA. In addition, protein kinase C (PKC) inhibitors such as H7 and sphingosine decreased the reduction of t-PA and the increase of PAI-1 by IL-1β and TNF-α. On the other hand, dibutryl cAMP and forskolin had no effect on the t-PA reduction and PAI-1 increase by IL-1β and TNF-α. Moreover, IL-1β and TNF-α did not cause [Ca²⁺] elevation. These results suggest that the inhibitory action of baicalein on the PAI-1 production by both cytokines might be directly mediated through PKC inhibition. © 1997 John Wiley & Sons, Ltd.     

Magnetic resonance imaging of esophageal squamous cell carcinoma using magnetite particles coated with anti-epidermal growth factor receptor antibody

A highly specific and effective magnetic resonance imaging (MRI) contrast agent was prepared by coating super-paramagnetite particles with monoclonal antibodies (MAbs) directed against epidermal growth factor receptors (EGFRs), which are over-expressed in esophageal squamous cell carcinoma. The preparation maintained both the immuno-reactivity of the MAbs and the full relaxing capability of the magnetite particles. The particles of this EGFR-specific contrast agent are 13.2 ± 1.9 nm in size, and thus, it is assumed that they are smaller than capillary pores and, hence, able to escape scavenging by reticulo-endothelial system cells. The EGFR-specific T2-relaxing ability of this contrast agent was ascertained first in vitro, using the EGFR-expressing cell line TE8 and the EGFR-deficient cell line H69. The results in athymic rats bearing TE8 or H69 tumors revealed that the agent has EGFR-specific MRI contrast capacity in vivo. The electron-microscopic findings in TE8 tumor-bearing rats revealed that the magnetite particles had been taken up by their lysosomes. In conclusion, immuno-specific MRI using magnetite particles coated with MAbs against EGFR appears to be useful in the diagnosis of squamous cell carcinoma of the esophagus. Int. J. Cancer 75:626–634, 1998. © 1998 Wiley-Liss, Inc.     

Chronic reduction in dietary tryptophan leads to changes in the emotional response to stress in mice

Acute depletion of brain tryptophan (TRP) levels in humans has been used as a biochemical model of depression. In this study, we examined the effects of consumption of a diet low in TRP on emotional behavior in mice. Specifically, we assessed various parameters of emotional behavior in mice fed a TRP-limited diet for at least 1 mo. TRP-limited mice showed increased defensive, but not offensive, aggression in the resident-intruder test. In the social dominance tube test, these mice showed enhanced social dominance. Since defensive aggression is thought to be a reflection of not only aggression but also fear, these changes in the social behavior of TRP-limited mice are thought to reflect changes in their emotional status. TRP-limited mice also showed increased locomotor activity and mobility in the open field and forced swim tests, respectively, suggesting that their stress/emotional responsiveness was enhanced. Importantly, these mice displayed normal levels of anxiety and motor performance as determined by the elevated zero maze and open field tests, and the rotarod test, respectively, suggesting that their hyperactivity was not due to a reduction in anxiety levels or to enhancement of their motor performance. Thus, dietary TRP restriction appears to result in alterations in the emotional response to stress, in mice.     

Perioperative music therapy with a key-lighting keyboard system in elderly patients undergoing digestive tract surgery

BACKGROUND/AIMS: It is important to minimize the perioperative mental dysfunction of elderly patients undergoing surgery and to avoid lowering their coping skills postoperatively. Music therapy for digestive tract surgery has yet not been explored. METHODOLOGY: We evaluated perioperative music therapy using a simple key-lighting keyboard system in 37 elderly patients who underwent digestive tract surgery (Group A) compared with 13 patients who were not applied music therapy (Group B). RESULTS: On the first day after surgery there were no general hemodynamic changes after music therapy. There were no significant changes in the Philadelphia Geriatric Center morale scale and the Yesavage depression scale between the day before surgery and 7 POD in both groups. The self-assessed visual analogue health scale and the number connection test worsened significantly from 58.9+/-14.6 and 159+/-47 to 42.3+/-14.6 and 199+/-51 (p<0.05), respectively, over this time in Group B, but it did not worsen significantly in Group A. The happiness score increased significantly from 3.9+/-1.1 to 4.6+/-1.2 (P<0.05) over this time in Group A, but it did not increase significantly in Group B. CONCLUSIONS: We conclude that the music therapy with a key-lighting keyboard system in elderly patients does not change postoperative hemodynamics and helps to maintain perioperative mental functioning.     

Combination treatment of transjugular retrograde obliteration and endoscopic embolization for portosystemic encephalopathy with esophageal varices

The treatment of chronic portosystemic encephalopathy with esophageal varices has not yet been established. We were able to control a case of chronic portosystemic encephalopathy with esophageal varices using a combination treatment of transjugular retrograde obliteration and endoscopic embolization. A 57-year-old man came to our hospital in a confused, apathetic and tremulous state. The grade of encephalopathy was II. The plasma ammonia level was abnormally elevated to 119 microg/dL, and the ICGR15 was 59%. Endoscopic examination revealed nodular esophageal varices with cherry-red spots. There were no gastric varices. Ultrasonography and CT revealed liver cirrhosis with a splenorenal shunt. We first applied endoscopic embolization for the esophageal varices before transjugular retrograde obliteration. We injected 5% ethanolamine oleate with iopamidol retrogradely into the esophageal varices and their associated blood routes under fluoroscopy and obliterated the palisade vein, the cardiac venous plexus and left gastric vein. Transjugular retrograde obliteration was performed 14 days after endoscopic embolization. Retrograde shunt venography visualized the splenorenal shunt and communicating route to the retroperitoneal vein. There was no communicating route to the azygos vein. After obliteration of the communicating route to the retroperitoneal vein with absolute ethanol, 5% ethanolamine oleate with iopamidol was injected into the splenorenal shunt as far as the root of the posterior gastric vein. After transjugular retrograde obliteration, the encephalopathy improved to grade 0 even without the administration of lactulose and branched-chain amino acid. The plasma ammonia level and ICGR15 were reduced to 62 microg/dL and 26%. We conclude that combination treatment of transjugular retrograde obliteration and endoscopic embolization is a rational, effective and safe treatment for chronic portosystemic encephalopathy complicated with esophageal varices.