Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models

<p>Abstract</p> <p>Background</p> <p>In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.</p> <p>Results</p> <p>Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.</p> <p>Conclusion</p> <p>Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.</p

Small-Group Counseling in a Modified Tinnitus Retraining Therapy for Chronic Tinnitus

ObjectivesThe authors have treated chronic tinnitus patients using a combination of a simplified tinnitus retraining therapy (TRT) and medications, which we called modified TRT. In this clinical setting, we have attempted small-group counseling to find a time-effective equivalent of individual counseling. The aim of the present study was to evaluate the effectiveness of small-group counseling by comparing the treatment outcomes between individual and small-group counseling.MethodsThe patients who had distressing chronic tinnitus with normal hearing or mild hearing loss were included. The subjects were placed into the small-group (group 1:4) or the individual (group 1:1) counseling group, and underwent a modified TRT composed of a single session of directive counseling and ambient sound stimulation. In addition, alprazolam (0.25 mg) and ginkgo biloba extract (80 mg) were administered orally to the subjects for 3 months. The 3- and 6- month outcomes were assessed using the follow-up rates and tinnitus severity scores: awareness, tinnitus handicap inventory (THI), loudness, annoyance, and effect on life. The treatment responses were classified as improvement, no changes, and worsening.Results Of the total 149 patients (77 in group 1:1; 72 in group 1:4), 104 patients completed the protocol at 3 months, and 55 patients at 6 months. The follow-up rates were similar in both groups. Over the period of 6 months, all scores declined significantly except the loudness score at 3 months in both groups. Treatment responses showed no between-group differences. The success rate based on THI was 70% in group 1:1, and 64% in group 1:4 at 6 months.ConclusionThe small-group counseling of our modified TRT was comparable to the individual counseling for tinnitus relief. We suggest that this protocol can be implemented effectively in any crowded otolaryngology clinics

The Efficacy of the Prophylactic Use of Octreotide after a Pancreaticoduodenectomy

This study was performed to analyze the efficacy of the prophylactic use of octreotide (Novartis, Stein, Switzerland) for pancreatic fistula following a pancreaticoduodenectomy. The medical records of 190 patients who underwent a pancreaticoduodenectomy at the Samsung Medical Center in Seoul, Korea between January 2000 and December 2002 were reviewed. Patients were divided into either the octreotide (n = 81) or control group (n = 109). The octreotide group received subcutaneous injections of 100 µg of octreotide every 12 hours for more than five days after surgery. The control group was not treated with octreotide. The criterion of pancreatic fistula was the drainage of the amylase rich fluid, over 500 U/mL in the three days after surgery. The morbidity and mortality rates were 32.1% and 1.2% in the octreotide group and 31.2% and 0% in the control group, respectively. Pancreatic fistula was the second most common complication (8.4%). In the univariate analysis, octreotide was ineffective in reducing pancreatic fistula (p = 0.26). However, in the multivariate regression analysis, combined gastrectomy (p = 0.018), cellular origin of the disease (p = 0.049), and use of octreotide (p = 0.044) were the risk factors that increased the frequency of pancreatic fistula. Therefore, the routine use of octreotide after a pancreaticoduodenectomy should be avoided until a worldwide consensus is established

Long Term Clinical Outcomes of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Single Center Study

Objectives Few studies have reported long-term follow-up after treatment of gastric mucosaassociated lymphoid tissue (MALT) lymphoma. In this single-center study, we investigated longterm treatment outcomes in patients diagnosed with gastric MALT lymphoma. Methods The study included 80 patients diagnosed with gastric MALT lymphoma, who were followed up at a single center between January 2005 and December 2019 after Helicobacter pylori eradication therapy, radiotherapy, or chemotherapy. We evaluated complete remission, improvement, or recurrence of the lesion. Follow-up over >60 months was classified as long-term follow-up, and the progression-free survival rate was recorded. Results Following H. pylori eradication treatment, complete remission occurred in 85.9% (55/64) of H. pylori-positive and 50.0% (3/6) of H. pylori-negative patients. All patients with gastric MALT lymphoma who did not respond to H. pylori eradication therapy (100.0% [6/6]) achieved complete remission following administration of local radiotherapy. We observed no deaths on long-term follow-up (>60 months), and the progression-free survival was 101 months. Conclusions In this study, patients with gastric MALT lymphoma showed excellent survival rates, progression-free survival, and prognosis on long-term follow-up. Prospective studies are warranted to determine the long-term prognosis of gastric MALT lymphoma after treatment

Prognostic Significance of Angiogenesis by Chalkley Counting in Node Negative Cancer of the Ampulla of Vater

Angiogenesis is essential for tumor growth and metastasis. Currently, the Chalkley assay with CD34 immunostaining is the proposed standard method for angiogenesis quantification in solid tumor sections. The purpose of this study was to evaluate the expression of CD34 and its prognostic significance using the Chalkley method in node negative carcinoma of the ampulla of Vater. Between January 1997 and December 2006, 56 node negative patients who had curative resection for carcinoma of the ampulla of Vater were retrospectively reviewed. The Chalkley count was expressed as the mean value of the three counts for each tumor and further divided into two groups according to the mean value of the Chalkley count: low < 4 or high ≥ 4. The mean Chalkley count value was 4.0 (± 3.1). In the low Chalkley group, the 1- and 3-yr recurrence rates were 18.3%, 47.6% respectively; in the high Chalkley group, the 1- and 3-yr recurrence rates were 26.5% and 60.6% respectively. Only high Chalkley count had statistical significance as a factor in recurrence of node negative ampulla of Vater carcinoma. Assessment of angiogenesis may have an important role in the prognostic evaluation of node negative cancer of the ampulla of Vater

Serum Vascular Endothelial Growth Factor in Pediatric Patients with Community-Acquired Pneumonia and Pleural Effusion

This study investigated the serum vascular endothelial growth factor (VEGF) levels in children with community-acquired pneumonia. Serum VEGF levels were measured in patients with pneumonia (n=29) and in control subjects (n=27) by a sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar pneumonia without pleural effusion (n=9) groups based on the findings of chest radiographs. We also measured serum IL-6 levels and the other acute inflammatory parameters. Serum levels of VEGF in children with pneumonia were significantly higher than those in control subjects (p<0.01). Children with lobar pneumonia with or without effusion showed significantly higher levels of serum VEGF than children with bronchopneumonia. For lobar pneumonia, children with pleural effusion showed higher levels of VEGF than those without pleural effusion. Children with a positive urinary S. pneumonia antigen test also showed higher levels of VEGF than those with a negative result. Serum IL-6 levels did not show significant differences between children with pneumonia and control subjects. Serum levels of VEGF showed a positive correlation with the erythrocyte sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one of the key mediators that lead to lobar pneumonia and parapneumonic effusion

A test of the submentalizing hypothesis : apes' performance in a false belief task inanimate control

Financial support came from Ministry of Education, Culture, Sports, Science and Technology (K-CONNEX to FK), Japan Society for Promotion of Science (KAKENHI 26885040, 16K21108 to FK), JSPS (KAKENHI 26245069, 24000001 to SH), and European Research Council (Synergy grant 609819 SOMICS to JC).Much debate concerns whether any nonhuman animals share with humans the ability to infer others' mental states, such as desires and beliefs. In a recent eye-tracking false-belief task, we showed that great apes correctly anticipated that a human actor would search for a goal object where he had last seen it, even though the apes themselves knew that it was no longer there. In response, Heyes proposed that apes' looking behavior was guided not by social cognitive mechanisms but rather domain-general cueing effects, and suggested the use of inanimate controls to test this alternative submentalizing hypothesis. In the present study, we implemented the suggested inanimate control of our previous false-belief task. Apes attended well to key events but showed markedly fewer anticipatory looks and no significant tendency to look to the correct location. We thus found no evidence that submentalizing was responsible for apes' anticipatory looks in our false-belief task.Publisher PDFPeer reviewe

GSK3B induces autophagy by phosphorylating ULK1

Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian homolog of the yeast kinase Atg1, has an essential role in autophagy induction. In nutrient and growth factor signaling, ULK1 activity is regulated by various posttranslational modifications, including phosphorylation, acetylation, and ubiquitination. We previously identified glycogen synthase kinase 3 beta (GSK3B) as an upstream regulator of insulin withdrawal-induced autophagy in adult hippocampal neural stem cells. Here, we report that following insulin withdrawal, GSK3B directly interacted with and activated ULK1 via phosphorylation of S405 and S415 within the GABARAP-interacting region. Phosphorylation of these residues facilitated the interaction of ULK1 with MAP1LC3B and GABARAPL1, while phosphorylation-defective mutants of ULK1 failed to do so and could not induce autophagy flux. Furthermore, high phosphorylation levels of ULK1 at S405 and S415 were observed in human pancreatic cancer cell lines, all of which are known to exhibit high levels of autophagy. Our results reveal the importance of GSK3B-mediated phosphorylation for ULK1 regulation and autophagy induction and potentially for tumorigenesis. © 2021, The Author(s).1