The effects of perinatal anoxia or hypoxia on hippocampal kindling development in rats

The effects of anoxia and hypoxia (3% oxygen) at 10–12 post days of age on the development of ventral hippocampal kindling and its transfer to the contralateral ventral hippocampus were studied in adult male Sprague-Dawley rats. During oxygen deprivation, the heart rate decreased to 15% of the prehypoxic value in the animals exposed to anoxia and 40% in those exposed to hypoxia. As is observed in asphyxia of human newborns, our study included both ischemia and hypoxia. The susceptibility to kindling, which was measured by kindling rate, afterdischarge threshold, generalized seizure threshold, and total afterdischarge duration to stage 5, had a tendency to be enhanced in rats exposed to hypoxia compared with controls. The facilitating effects on primary site kindling were enhanced in the animals exposed to hypoxia compared with those exposed to anoxia. Transfer, which was indicated by kindling rate and afterdischarge threshold, was also slightly facilitated in the rats exposed to anoxia or hypoxia in the perinatal period. These results reveal that perinatal oxygen deficiency may not be sufficient to lead to the development of temporal lobe epilepsy. However, it is possible that perinatal hypoxia results in some pathophysiological change in the brain which leads to greater seizure susceptibility in adulthood.     

Cellular roles in physiological root resorption of deciduous teeth in the cat

This study has attempted to assess the importance of mesenchymal cells, fibroblasts, cementoblasts, and mononuclear phagocytes (i.e., macrophages) in physiological root resorption of feline deciduous teeth. Deciduous incisors of three- to six-month-old kittens undergoing root resorption were investigated by means of electron microscopy. In an early phase of root resorption, the resorption organ consisted of many fibroblasts and relatively few macrophages and odontoclasts, the last with a wide, clear zone and narrow, immature, ruffled border. In the active phase of root resorption, the resorption organ contained many odontoclasts with a well-developed ruffled border and a reduced clear zone, cementoblasts, fibroblasts, macrophages, neutrophils, and many blood vessels. Cementoblasts were present usually on the resorbing dentin surface adjacent to odontoclasts and, in many cases, these cells communicated with each other via gap junctions. Cementoblasts frequently extended broad cell processes with secretion granules and with phagosomes containing collagen fibrils into the dentinal tubules exposed to resorption lacunae. Some macrophages exhibiting a clear zone-like structure also appeared on resorbing dentin surfaces. In the resting phase of root resorption, the dentin surface was covered mostly with cementoblasts resembling bone lining cells. There was an occasional macrophage, but no odontoclasts were observed during this phase. During removal of the periodontal ligament concomitant with root resorption, many fibroblasts phagocytosed mature collagen fibrils, as well as amorphous fluffy material. These results suggest that these mesenchymal cells, as well as odontoclasts, are essential for the cellular removal of dental hard and soft tissues during shedding of feline deciduous teeth.     

Technical evaluation of dialysate flow in a newly designed dialyzer

Rexeed was developed by Asahi Kasei Medical using wave-shaped hollow fibers, a full baffle, and a short taper housing to improve dialysate flow. The present study is clarifies improvement in dialysate flow with Rexeed-15 compared with that of a conventional dialyzer. Dialysate flow was evaluated by the pulse-response method. Dialysate pressure and tracer concentration were measured at a blood-side flow rate (QBeta) of 200 ml/min, a dialysate-side flow rate (QD) of 500 ml/min, and a net filtration rate (QF) of 0 ml/min using needles placed in the test dialyzer. Dialyzer performance was evaluated by measuring urea and vitamin B12 clearance at QB = 200 and 400 ml/min, QD = 300-800 ml/min, and QF = 0 ml/min. In the conventional dialyzer, dialysate channeling was observed. In contrast, Rexeed-15 had a uniform dialysate flow. Urea and vitamin B12 clearance with Rexeed-15 was slightly sensitive to QD. The overall mass transfer coefficient for urea with Rexeed-15 was more than 50% higher than that of the conventional dialyzer, indicating the possibility of reduced dialysate usage with Rexeed. Rexeed has a highly optimal dialysate flow, due to the wave-shaped hollow fibers and the new housing, and gives increased clearance for lower-molecular-weight substances.     

Balloon-occluded retrograde transvenous obliteration using a new microballoon for gastric varices

We here present a case involving a complicated type of gastric fundal varices treated by balloon-occluded retrograde transvenous obliteration. A newly developed 1.8-Fr tip coaxial microballoon catheter was successfully advanced into narrow and tortuous varices, and a sclerosant could be infused in a reasonable manner, avoiding reflux into collaterals. Divided injections of sclerosant were performed over two days, via a microballoon catheter that remained inserted overnight with balloon inflation, and the sclerosant could be infused sufficiently in the entirety of the varices. The varices were completely thrombosed and prominently reduced.     

Resection of a locally advanced hilar tumor and the hepatic artery after stepwise hepatic arterial embolization： A case report

We herein report a case of a hilar tumor with extensive invasion to the proper hepatic artery, which was successfully treated with a radical resection in a 57-year-old female patient after a stepwise hepatic arterial embolization. She underwent right colectomy and partial hepatectomy for advanced colon cancer two years ago and radiofrequency ablation therapy for a liver metastasis one year ago, respectively. A recurrent tumor was noted around the proper hepatic artery with invasion to the left hepatic duct and right hepatic artery 7 mo previously. We planned a radical resection for the patient 5 mo after the absence of tumor progression was confirmed while he was undergoing chemotherapy. To avoid surgery-related liver failure, we tried to promote the formation of collateral hepatic arteries after stepwise arterial embolization of the posterior and anterior hepatic arteries two weeks apart. Finally, the proper hepatic artery was occluded after formation of collateral flow from the inferior phrenic and superior mesenteric arteries was confirmed. One month later, a left hepatectomy with hepatic arterial resection was successfully performed without any major complications.     

Direct regulation of transforming growth factor β‐induced epithelial–mesenchymal transition by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells

Transforming growth factor β (TGFβ) causes the acquisition of epithelial–mesenchymal transition (EMT). Although the tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) can negatively regulate many signaling pathways activated by TGFβ, hyperactivation of these signaling pathways is observed in lung cancer cells. We recently showed that PTEN might be subject to TGFβ‐induced phosphorylation of its C‐terminus, resulting in a loss of its enzyme activities; PTEN with an unphosphorylated C‐terminus (PTEN4A), but not PTEN wild, inhibits TGFβ‐induced EMT. Nevertheless, whether or not the blockade of TGFβ‐induced EMT by the PTEN phosphatase activity might be attributed to the unphosphorylated PTEN C‐terminus itself has not been fully determined. Furthermore, the lipid phosphatase activity of PTEN is well characterized, whereas the protein phosphatase activity has not been determined. By using lung cancer cells carrying PTEN domain deletions or point mutants, we investigated the role of PTEN protein phosphatase activities on TGFβ‐induced EMT in lung cancer cells. The unphosphorylated PTEN C‐terminus might not directly retain the phosphatase activities and repress TGFβ‐induced EMT; the modification that keeps the PTEN C‐terminus not phosphorylated might enable PTEN to retain the phosphatase activity. PTEN4A with G129E mutation, which lacks lipid phosphatase activity but retains protein phosphatase activity, repressed TGFβ‐induced EMT. Furthermore, the protein phosphatase activity of PTEN4A depended on an essential association between the C2 and phosphatase domains. These data suggest that the protein phosphatase activity of PTEN with an unphosphorylated C‐terminus might be a therapeutic target to negatively regulate TGFβ‐induced EMT in lung cancer cells.     

Verification of Tokyo Guidelines for diagnosis and management of acute cholangitis

Background

This study aimed to verify diagnostic criteria and severity assessment of the Tokyo Guidelines for acute cholangitis.

Methods

We re-examined whether acute cholangitis was concomitant with gallstones according to the Tokyo Guidelines in 248 patients with choledocholithiasis. Our conventional diagnoses based on physician decision were compared with diagnoses from the Tokyo Guidelines. Problems with severity grade criteria were also evaluated.

Results

In total, 53 cases of acute cholangitis were determined by using the Tokyo Guidelines, including three false-negative and seven false-positive cases (acute cholecystitis or pancreatitis was concomitant with choledocholithiasis). Sensitivity, specificity, and accuracy were 94%, 96%, and 96%, respectively. Forty of the 53 patients underwent biliary drainage (mean interval between admission and drainage, 1.4 days). Severity grades were mild in 10, moderate in 30, and severe in 13 patients. Of these 13 patients with severe disease, 2 had chronic renal failure, 1 had liver cirrhosis, and 1 had severe acute pancreatitis and liver cirrhosis. No patients died, irrespective of severity grade.

Conclusions

Acute cholangitis should be carefully diagnosed when other inflammatory disease is concomitant with choledocholithiasis. A few patients have absolute acute cholangitis even when they do not meet Tokyo Guidelines diagnostic criteria. Classification into mild or moderate grade using the Tokyo Guidelines is difficult when early biliary drainage is routinely performed. When determining severity grade, clinicians must distinguish between organ dysfunction associated with cholangitis itself and that associated with the underlying/concomitant disease. Apart from a few problems like these, the Tokyo Guidelines are mostly acceptable for the diagnosis and management of acute cholangitis.     

Development of orf virus as a bifunctional recombinant vaccine: surface display of Echinococcus granulosus antigen EG95 by fusion to membrane structural proteins

The parapoxvirus, orf virus (ORFV) causes superficial skin lesions in infected sheep. Unattenuated ORFV is used globally to vaccinate against orf. Recombinant poxviruses are proven delivery systems and we investigated strategies to express the immunogenic Echinococcus granulosus peptide EG95 from ORFV with the aim of developing a recombinant bivalent vaccine. EG95 is an oncosphere protein of the cestode E. granulosus, a parasite responsible for causing cystic hydatid disease in a wide range of hosts including humans and grazing animals such as sheep. Recombinant viruses were produced in which EG95 was expressed by itself or fused to ORFV envelope-associated structural proteins 10 kDa and F1L. Infection studies in sheep showed that specific antibodies were produced against ORFV and EG95 and that the antibody levels against EG95 were comparable to that of animals immunized with purified EG95 in Quil A adjuvant, an immunization regime that is known to afford protection. A single exposure to the dual vaccine has potential for protecting lambs against orf and for priming against EG95 so as to respond strongly to a later injection of EG95 protein.     

Social epidemiology and Eastern Wisdom

Social epidemiology is the field of study that attempts to understand the social determinants of health and the dynamics between societal settings and health. In the past 3 decades, large-scale studies in the West have accumulated a range of measures and methodologies to pursue this goal. We would like to suggest that there may be conceptual gaps in the science if Western research models are applied uncritically in East Asian studies of socioeconomic, gender, and ethnic inequalities in health. On one hand, there are common concerns, including population aging and gendered labor market participation. Further, international comparison must be built on shared concepts such as socioeconomic stratification in market economies. On the other hand, some aspects of health, such as common mental disorders, may have culturally specific manifestations that require development of perspectives (and perhaps novel measures) in order to reveal Eastern specifics. Exploring and debating commonalities and differences in the determinants of health in Oriental and Occidental cultures could offer fresh inspiration and insight for the next phase of social epidemiology in both regions.