Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

Substrains of the Spontaneously Hypertensive rat (SHR), a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD), have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD). However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA) test, and its response on the conditioned place preference (CPP) paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj). Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine

Lactobacillus acidophilus Contributes to a Healthy Environment for Vaginal Epithelial Cells

Lactobacillus species in the female genital tract are thought to act as a barrier to infection. Several studies have demonstrated that lactobacilli can adhere to vaginal epithelial cells. However, little is known about how the adherence of lactobacilli to vaginal epithelial cells affects the acidity, cell viability, or proliferation of the lactobacilli themselves or those of vaginal epithelial cells. Lactobacillus acidophilus was co-cultured with immortalized human vaginal epithelial cells (MS74 cell line), and the growth of L. acidophilus and the acidity of the culture medium were measured. MS74 cell density and viability were also assessed by counting cell numbers and observing the cell attachment state. L. acidophilus showed exponential growth for the first 6 hr until 9 hr, and the pH was maintained close to 4.0-5.0 at 24 hr after culture, consistent with previous studies. The growth curve of L. acidophilus or the pH values were relatively unaffected by co-culture with MS74 cells, confirming that L. acidophilus maintains a low pH in the presence of MS74 cells. This co-culture model could therefore potentially be used to mimic vaginal conditions for future in vitro studies. On the other hand, MS74 cells co-cultured with L. acidophilus more firmly attached to the culture plate, and a higher number of cells were present compared to cells cultured in the absence of L. acidophilus. These results indicate that L. acidophilus increases MS74 cell proliferation and viability, suggesting that lactobacilli may contribute to the healthy environment for vaginal epithelial cells

Black hole as an Information Eraser

We discuss the identity of black hole entropy and show that the first law of black hole thermodynamics, in the case of a Schwarzschild black hole, can be derived from Landauer's principle by assuming that the black hole is one of the most efficient information erasers in systems of a given temperature. The term "most efficient" implies that minimal energy is required to erase a given amount of information. We calculate the discrete mass spectra and the entropy of a Schwarzschild black hole assuming that the black hole processes information in unit of bits. The black hole entropy acquires a sub-leading contribution proportional to the logarithm of its mass-squared in addition to the usual mass-squared term without an artificial cutoff. We also argue that the minimum of the black hole mass is $\sqrt{\log 2/(8\pi)}M_P$.Comment: 12 pages, 4 figures, minor change

Effect of high cobalt concentration on hopping motion in cobalt manganese spinel oxide (CoxMn3–xO4,x≥ 2.3)

Hopping motions in cobalt manganese spinel oxides with high cobalt concentration (CoxMn3−xO4, 2.3 ≤ x ≤ 2.7) are investigated in order to clarify the origin of unusual electrical behaviors as negative temperature coefficient (NTC) thermistors. Based on the resistance versus temperature (R−T) characteristics, hopping conduction mechanisms in MCO compounds (x = 2.3 and 2.5) are attributed to variable range hopping (VRH) motion with a parabolic distribution of the density of states (DOS) near the Fermi level. However, when Co content increases up to 2.7, transition in the hopping motion occurs from VRH to the nearest neighboring hopping (NNH) motion, which can be responsible for a huge increase of the resistance accompanied by decrease of the factor of thermal sensitivity (B value) in MCO compounds (x = 2.7). Also, hopping distance and activation energies for MCO (x = 2.3 and 2.5) compounds following VRH conduction are calculated as a function of temperature, indicating that higher B value observed in MCO (x = 2.5) compound is due to the larger hopping distance compared to that of MCO (x = 2.3) compound

p75 neurotrophin receptor regulates energy balance in obesity

Obesity and metabolic syndrome reflect the dysregulation of molecular pathways that control energy homeostasis. Here, we show that the p75 neurotrophin receptor (p75NTR) controls energy expenditure in obese mice on a high-fat diet (HFD). Despite no changes in food intake, p75NTR-null mice were protected from HFD-induced obesity and remained lean as a result of increased energy expenditure without developing insulin resistance or liver steatosis. p75NTR directly interacts with the catalytic subunit of protein kinase A (PKA) and regulates cAMP signaling in adipocytes, leading to decreased lipolysis and thermogenesis. Adipocyte-specific depletion of p75NTR or transplantation of p75NTR-null white adipose tissue (WAT) into wild-type mice fed a HFD protected against weight gain and insulin resistance. Our results reveal that signaling from p75NTR to cAMP/PKA regulates energy balance and suggest that non-CNS neurotrophin receptor signaling could be a target for treating obesity and the metabolic syndrome

APE1 Promotes Pancreatic Cancer Proliferation through GFRα1/Src/ERK Axis-Cascade Signaling in Response to GDNF

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer

Protective Effect of Heat Shock Protein 70 Against Oxidative Stresses in Human Corneal Fibroblasts

We evaluated DNA protection effect of heat shock protein (HSP) against cytotoxic effects of exogenous nitric oxide (NO) and reactive oxygen intermediate (ROI). Cultured human corneal fibroblasts were divided into 4 groups. Control (Group I) was not exposed to a sub-lethal heat treatment. Other 3 groups were exposed to 43℃ for 1 hr, then incubated at 37℃ during different duration (1, 6, 24 hr, Group II, III, IV, respectively). Expression pattern of HSP 70 was analyzed by Western blot. Cell viability was measured by MTT assay and the relationship between HSP 70 expression and DNA damage was examined by terminal deoxyribonucleotidyl transferase mediated dUTP-digoxigenin nick and labeling (TUNEL) stain and single cell gel electrophoresis. Expression pattern of HSP 70 was dependent on recovery times. Cell viability following heat treatment was significantly increased and the TUNEL positive cell number was decreased at 6 hr. In single cell gel electrophoresis, tail moments were increased in a dose-dependent manner by SNAP and X/XO. Following heat treatment, tail moments showed decreased significantly at 6 hr. These results suggest that induction of HSP 70 by sub-lethal heat treatment is closely related with cytoprotective effects against oxidative stresses in human corneal fibroblasts

Acute Appendicitis in Henoch-Schönlein Purpura : A Case Report

Common complications of Henoch-Schönlein purpura (HSP) that lead to surgical intervention include intussusception, perforation, necrosis, and massive gastrointestinal bleeding. Acute appendicitis is rarely seen as a complication of HSP. A seven-year-old boy was admitted for arthralgia, abdominal pain, hematochezia, melena, and purpuric rash on the lower extremities. On admission day abdominal ultrasonography was normal, but on day 5, he became pyrexial and developed right iliac fossa pain and tenderness with guarding. Ultrasonography showed distended appendix surrounded by hyperechoic inflamed fat. On exploration an acutely inflamed, necrotic appendix was removed and grossly there was an appendiceal perforation in the appendiceal tip. Microscopically some of the small blood vessels in the submucosa showed fibrinoid necrosis with neutrophilic infiltrations. The authors report the case of a child who developed acute perforative appendicitis requiring appendectomy while on treatment for HSP

Endovascular Treatment of Arterial Steno-Occlusive Lesions in Symptomatic Moyamoya Disease

The efficacy and safety of endovascular treatment (EVT) for moyamoya disease (MMD) have rarely been investigated. The objective of this study was to summarize the clinical outcomes of EVT for MMD and determine the potential role of EVT in treating symptomatic steno-occlusive lesions in MMD. Reports from January 2000 to December 2021 describing EVT in MMD were collected through a literature search. The search terms included “moyamoya”, “stent”, “angioplasty”, and “endovascular”. Data regarding baseline demographics, previous medical history, treated vessel, periprocedural complications, and angiographical recurrence were retrieved. This review included 10 studies with details of 19 patients undergoing a total of 31 EVT procedures. Twenty-one EVTs were performed as initial treatments for MMD, and 10 were performed as additional treatments for angiographical recurrence. The mean follow-up period of the initial EVTs was 9.0±11.9 months, with angiographical recurrence in 11 (68.8%) cases. The mean follow-up period of additional EVTs was 4.3±3.9 months, and seven (70.0%) EVTs showed restenosis of the re-treated vessel. Across all initial and additional EVTs, there were no differences in characteristics between the recurrence and non-recurrence groups. Overall, two periprocedural complications (9.5%) occurred, one vessel rupture and one massive intracerebral hemorrhage with subarachnoid hemorrhage. EVT plays a limited role in the management of symptomatic intracranial arterial steno-occlusive lesions of MMD. Recent advances in understanding the pathomechanism of MMD may urge neuro-interventionists to find a new endovascular approach with better balloon angioplasty or stenting mechanisms