c-Jun and the transcriptional control of neuronal apoptosis

There has been considerable interest in the molecular mechanisms of apoptosis in mammalian neurons because this form of neuronal cell death is important for the normal development of the nervous system and because inappropriate neuronal apoptosis may contribute to the pathology of human neurodegenerative diseases. The aim of recent research has been to identify the key components of the cell death machinery in neurons and understand how the cell death programme is regulated by intracellular signalling pathways activated by the binding of neurotrophins or death factors to specific cell surface receptors. The aim of this commentary was to review research that has investigated the role of the Jun N-terminal kinase (JNK)/c-Jun signalling pathway in neuronal apoptosis, focusing in particular on work carried out with developing sympathetic neurons. Experiments with sympathetic neurons cultured in vitro, as well as with cerebellar granule neurons and differentiated PC12 cells, have demonstrated that JNK/c-Jun signalling can promote apoptosis following survival factor withdrawal. In addition, experiments with Jnk(-/-) knockout mice have provided evidence that Jnk3 may be required for apoptosis in the hippocampus in vivo following injection of kainic acid, an excitotoxin, and that Jnk1 and Jnk2 are required for apoptosis in the developing embryonic neural tube. However, in the embryonic forebrain, Jnk1 and Jnk2 have the opposite function and are necessary for the survival of developing cortical neurons. These results suggest that JNKs and c-Jun are important regulators of the cell death programme in the mammalian nervous system, but that their biological effects depend on the neuronal type and stage of development.     

Efficacy of Biomist 30:30 and Aqua Reslin against Anopheles quadrimaculatus in Arkansas

Aqua Reslin and Biomist 30:30 technical permethrin and piperonyl butoxide were applied via ground ultra-low volume at a rate of 237 ml/min and 0.00196 kg active ingredient/ha against wild-caught adult Anopheles quadrimaculatus. The 2 formulations did not differ significantly at 31 m from the spray path (P < or = 0.05). However, at 61 and 91 m, percent mortality for 30:30 was significantly higher than for Aqua Reslin at each time after treatment (P < or = 0.05). Between 12 and 24 h, about 8% recovery was observed in mosquitoes treated with Aqua Reslin at 31 m.     

Management of choroidal neovascularization following laser photocoagulation for central serous chorioretinopathy

Little is known about the natural history and management of choroidal neovascularization (CNV) which developed as a complication of laser photocoagulation for central serous chorioretinopathy (CSC). We experienced two patients with CNV which developed after laser treatment for CSC. Submacular membranectomy was performed on both cases after the confirmation of subretinal CNV with optical coherence tomography. One patient received photodynamic therapy for recurrent CNV. The vision of both patients has been improved over 6 months of follow up. These cases suggest that active intervention, including submacular surgery, improves the visual prognosis of this condition.     

A case of streptococcus pyogenes endophthalmitis following cataract surgery

A small number of cases of bacterial endophthalmitis due to Streptococcus pyogenes, a Gram positive organism, have previously been reported. In this case, rapidly progressive Streptococcus pyogenes endophthalmitis was developed five years after cataract surgery which had been. The previous cataract surgery was combined with intraocular lens implantation by trans-scleral suspension technique. Treatment included enucleation and intravenous antibiotic injection. In this case of delayed Streptococcus pyogenes endophthalmitis after extracapsular cataract extraction. It seems probable that progressive erosion of the suture material resulted in exogenous endophthalmitis.     

Possible role of ginsenoside Rb1 on regulation of rat liver triglycerides

We have studied the effects of ginsenoside Rb1 (GRb1) on the change in lipid contents in rat liver. When GRb1 was administered intraperitoneally to rats, liver microsomal cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were lower than those in control rats. The contents of triglyceride (TG) and cholesterol were decreased, but those of total phospholipid, phosphatidylcholine, and phosphatidylethanolamine were increased in the GRb1-treated group compared with controls. These results indicate that GRb1 might be involved in lipid metabolism by regulating the activity of microsomal cytochrome P-450 monooxygenase. Although liver TG levels were reduced by GRb1, the levels of TG and beta-lipoprotein in serum from the GRb1-treated group did not change as compared with those in controls. Thus we suggest that the decrease in liver TG levels with GRb1-treatment is not associated with the secretion of TG-rich very low-density lipoprotein. Furthermore, the level of cAMP was also significantly increased in the GRb1-treated group as compared with that in controls. Additionally, the cAMP level was more markedly increased as compared with that in the GRb1-treated group or control group when GRb, was exogenously added to the reaction system for measuring cAMP production in homogenates from control group liver. Accordingly, these results demonstrate that GRb1 might lower TG levels via cAMP-production in the liver, and GRb1 might be an interesting candidate to for a modulator of cAMP-mediated effects, especially within the liver steatosis system.     

Off-pump coronary artery bypass with complete avoidance of aortic manipulation

BACKGROUND: Off-pump coronary artery bypass (OPCAB) with complete avoidance of aortic manipulation may further reduce perioperative morbidity in addition to the benefits achieved by avoiding cardiopulmonary bypass and cardioplegic arrest. METHODS: We prospectively analyzed 222 consecutive patients with multivessel disease who underwent OPCAB without aortic manipulation (group I), and compared them with 123 consecutive patients who underwent OPCAB using additional free arterial or saphenous vein grafts that were anastomosed on the ascending aorta (group II) and 76 consecutive patients who underwent on-pump conventional coronary artery bypass grafting (group III). RESULTS: No significant differences were noted in operative mortalities among the three groups (2/222, 3/123, and 2/76 in groups I, II, and III, respectively; p = NS). Fewer distal anastomoses were done in group I compared with groups II and III (3.2 +/- 0.9, 3.5 +/- 0.8, and 3.7 +/- 0.9 in groups I, II, and III, respectively; p < 0.001). No differences were noted in the incidences of postoperative morbidities such as mediastinitis, pulmonary complication, and reoperation for bleeding. The incidences of stroke, atrial fibrillation, and acute renal failure were significantly lower in group I than in group III (p < 0.05), although there were no significant differences between groups II and III. The incidence of perioperative myocardial infarction was significantly lower in group I than in groups II and III (p < 0.05), although there was no significant difference between groups II and III. CONCLUSIONS: Our results demonstrate that OPCAB with complete avoidance of aortic manipulation may further reduce the incidence of perioperative morbidities such as stroke, atrial fibrillation, acute renal failure, and perioperative myocardial infarction.     

How correctly does an intramedullary rod represent the longitudinal tibial axes?

In a robot-assisted procedure for preparing the tibia in total knee arthroplasty, developed in the authors' laboratory, an intramedullary rod is used to register the tibia. In 18 formalin-fixed tibias, the difference in orientation was calculated between the intramedullary rod and several longitudinal tibial axes used in clinical practice. This was done using roentgenstereophotogrammetric analysis. Three tibial axes and two insertion techniques were considered. In three-dimensional space, small differences between the axes are observed. The results showed a high standard deviation, indicating the importance of anatomic differences. In the frontal plane, the difference in orientation between rod and tibial axes never exceeded +/- 2 degrees. In the sagittal plane, the observed differences were larger. Significant differences between the considered axes appeared. The results of the two insertion techniques were not significantly different. Because an intramedullary rod frequently is used for alignment of the tibia in conventional surgery, these results also are valuable for conventional surgery. In the current study, the accuracy of the intramedullary alignment is examined, without influences of the sawing procedure. Moreover, the study is not limited to the frontal plane; the total accuracy in three-dimensional space, and the accuracy in the frontal and the sagittal planes were studied.     

Shock wave therapy ineffective for plantar fasciitis

Extracorporeal shock wave therapy (ESWT) cannot be recommended to improve pain and function in patients with plantar fasciitis based on the results of this study. Although previous studies do report a benefit from ESWT, this study appears to represent a higher level of evidence than was previously available for evaluating the efficacy of this therapy. An updated meta-analysis combining all the studies on ESWT will be useful.     

Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease

Ulcerative colitis (UC) is a chronic inflammatory disease that produces reactive oxygen and nitrogen species and increases the risk of colorectal cancer (CRC). The p53 tumor suppressor gene is frequently mutated in UC-associated dysplastic lesions and CRC. We are exploring the hypothesis that p53 mutations in the nontumorous colonic tissue in noncancerous UC cases indicate genetic damage from exposure to exogenous and endogenous carcinogens and may identify individuals at increased cancer risk. We are reporting, for the first time, the frequency of specific p53 mutated alleles in nontumorous colon tissue from donors either with or without UC by using a highly sensitive genotypic mutation assay. Higher p53 mutation frequencies of both G:C to A:T transitions at the CpG site of codon 248 and C:G to T:A transitions at codon 247 were observed in colon from UC cases when compared with normal adult controls (P = 0.001 and P = 0.001, respectively). In the UC cases, higher p53 codon 247 and 248 mutation frequencies were observed in the inflamed lesional regions when compared with the nonlesional regions of their colon (P < 0.001 and P = 0.001). The colonic nitric oxide synthase-2 activity was higher in UC cases than in non-UC adult controls (P = 0.02). Our data are consistent with the hypothesis that a higher frequency of p53 mutant cells can be generated under oxidative stress in people with UC. The increased frequency of specific p53 mutated alleles in noncancerous UC colon tissue may confer susceptibility to the development of CRC in an inflammatory microenvironment.