Targeting the hedgehog signaling pathway with interacting peptides to Patched-1

Background  

The hedgehog (Hh) signaling pathway is aberrantly activated in many cancers. Overproduction of sonic hedgehog (Shh), a ligand in the Hh pathway, increases Hh signaling activity by inhibiting Patched-1 (Ptch1), a suppressive receptor in the Hh pathway. The purpose of this study was to establish a novel strategy for treating pancreatic cancer and other Hh-dependent cancers through control of the tumor-suppressive function of Ptch1.     

Association between ApoE phenotypes and telomere erosion in Alzheimer's disease

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.     

Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease

Aim: Recent studies have shown that some antihypertensive medications are associated with a significant reduction in the incidence of Alzheimer's disease (AD). However, it remains uncertain whether antihypertensive drugs may have a preventive effect on cognitive decline in patients with AD. We investigated the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator‐activated receptor γ‐stimulating activity, on cognition and regional cerebral blood flow (rCBF) in elderly hypertensive patients with AD. Methods: A total of 20 patients with probable AD and essential hypertension were randomly assigned to the telmisartan group (n = 10, 40–80 mg daily) or the amlodipine group (n = 10, 5–10 mg daily) for 6 months. Results: The groups had a similar significant reduction in systolic and diastolic blood pressure after treatment. The telmisartan group did not show any changes in cognitive function test scores, while the amlodipine group showed significantly higher scores on the AD Assessment Scale‐Cognitive Subscale (Japanese version). Analysis of covariance to analyze treatment effect revealed that the telmisartan group showed increased rCBF in the right supramarginal gyrus, superior parietal lobule, cuneus, and lingual gyrus compared with the amlodipine group, while the amlodipine group showed increased rCBF only in the right cingulate gyrus compared with the telmisartan group at 6 months. Conclusion: These findings suggest that telmisartan may have additional benefits and be useful for the treatment of elderly hypertensive patients with AD. Geriatr Gerontol Int 2012; 12: 207–214.     

Relationship between the preoperative body mass index and the resolution of metabolic syndrome following Roux-en-Y gastric bypass

BACKGROUND: The increased prevalence of overweight and obesity has reached alarming proportions worldwide and has serious health implications, including an association with an increase in metabolic syndrome. Among the methods to control metabolic syndrome, bariatric surgery plays an important role and can provide a significant improvement in the components of metabolic syndrome. Objective: The aim of this study was to determine the relationship between the preoperative body mass index (BMI) and the postoperative resolution of metabolic syndrome [using the National Cholesterol Education Program (NCEP ATP III criteria)] in patients undergoing Roux-en-Y gastric bypass (RYGB). Methods: Retrospective analysis of a consecutive series of cases, stratified by BMI into three groups (group 1, BMI <40 kg/m(2), group 2, BMI 40-49.9 kg/m(2), and group 3, BMI 50 ≥ kg/m(2)) consisting of both sexes between 20 and 60 years of age. The cohort consisted of 149 patients undergoing RYGB. Anthropometric, biochemical, and clinical evaluations were performed preoperatively and then at 30 and 180 days postoperatively. Results: The average age was 40 years, and the patients were predominately female (72%). At the end of the study period, all groups showed a significant reduction in metabolic syndrome compared with preoperative levels. Logistic regression showed a higher percentage of metabolic syndrome in patients in group 3 after 180 days. Conclusion: There was significant resolution of metabolic syndrome in all groups, independently of the preoperative BMI. However, in group 3 (BMI ≥ 50 kg/m(2)), 22% of individuals still presented with metabolic syndrome at 180 days postoperatively (P=0.03).     

Carbonization of cellulose cell wall evaluated with ultraviolet microscopy

This is the first study of cellulose carbonization in the interior of cell walls. Cotton cellulose was pyrolyzed under nitrogen or in aromatic solvents (benzophenone, diphenyl sulfide, and 1,3-diphenoxybenzene) at 280 °C, and cross sections of the cell walls were examined using ultraviolet (UV) microscopy. After pyrolysis under nitrogen, UV absorption caused by carbonization appeared inside the cell walls. The absorptivity of the cell interiors was homogeneous and slightly lower than that of the cell surfaces. The UV spectra had maximal absorption at ca. 250 nm. The spectra of model compounds and Py-GC/MS analysis data suggested that furanic and polycyclic aromatic structures were present in the carbonized products. The use of aromatic solvents decreased the yields of solid carbonized products and the UV absorptivity, which remained homogeneous throughout the cross sections. The mechanism of cellulose carbonization in cell walls is discussed along with the influence of aromatic solvents.

This is the first study of cellulose carbonization in the interior of cell walls.     

The clinical manifestations of lumbar disease are correlated with self-rating depression scale scores

Background

Depression can exacerbate symptoms of chronic pain and worsen disability. The symptoms of lumbar disease may be particularly sensitive to psychological state, but statistical associations between low back pain (LBP) severity and mental health status have not been established.

Methods

Of the 151 patients with LBP, 122 completed questionnaires probing depressive symptoms, LBP severity, and degree of disability. In addition to completing self-report questionnaires, patients provided demographic and clinical information. A self-rating depression scale (SDS) was used to screen for depression. Pain and disability were assessed by the visual analog scale (VAS) and the Roland–Morris disability questionnaire (RDQ), respectively. Overall clinical severity was assessed using the Japanese Orthopaedic Association (JOA) score. Kendall’s tau correlation coefficients were calculated to examine the relationships among these variables.

Results

Ninety-four patients (77 %) were in a depressive state as indicated by SDS score ≥40, including mild depression group (47 patients, SDS score from 40 to 49) and depression group (47 patients, SDS score ≥50). There were only 28 patients in the no depression group (SDS score ≤39). There was no significant difference in both age and pain duration among the three groups. The mean VAS score in the depression group (70 ± 19 mm) was higher than both no depression (41 ± 24 mm) and mild depression groups (52 ± 21 mm). The mean JOA score in the no depression group (14 ± 5.0 points) was higher than both mild depression (12 ± 4.0 points) and depression groups (10 ± 6.0 points). The mean RDQ in the depression group (15.1 ± 6.0 points) was higher than both no depression (6.4 ± 5.0 points) and mild depression groups (10.9 ± 5.4 points). Factors significantly correlated with SDS score included VAS, JOA score, and RDQ score. In contrast, SDS did not correlate with patient age or pain duration.

Conclusions

The majority of chronic LBP patients examined were in a depressed state and the severity of depression correlated with pain severity, degree of self-rated disability, and clinical severity.     

Alice in Wonderland syndrome associated with mycoplasma infection

Alice in Wonderland syndrome (AIWS) is a rare condition in which patients report distorted size perception of objects and their own bodies. Although specific causes and pathology have not been elucidated, an association between AIWS and infection has been suggested. To our knowledge, mycoplasma‐induced AIWS has not been examined. A girl aged 7 years 11 months presented with fever (temperature, 40°C) and cough. Although the fever disappeared after approximately 10 days, she complained that her mother's face suddenly appeared smaller to her. Subsequently, she complained that objects intermittently appeared smaller than normal. Particle agglutination test indicated elevated serum antibodies against Mycoplasma pneumoniae. The patient was therefore diagnosed the patient with AIWS secondary to mycoplasma infection. Although mycoplasma infection is known to cause various central nervous system symptoms, this is the first report involving AIWS, suggesting that mycoplasma could affect visual function in children.