Inhibition of milk ingestion and growth after administration of a neutral cannabinoid CB1 receptor antagonist on the first postnatal day in the mouse

We have shown previously that neonatal exposure to the cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (SR141716) interfered with suckling and development. However, it was not clear whether the developmental deficiencies were induced by neutral CB1 receptor blockade, thereby inhibiting endogenous cannabinoid "tone," or by inverse agonist reduction of constitutive CB1 receptors. CB1 receptor blockade supports our hypothesis that low CB1 receptor concentrations and/or reduced endocannabinoid levels underlie infant nonorganic failure to thrive (NOFTT). Inverse agonism implies that lower constitutive CB1 receptor activity may be responsible for impaired food intake in newborns. In the present study, we injected the neutral CB1 receptor antagonist 5-(4-chlorophenyl)-3-[(E)-2-cyclohexylethenyl]-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole (VCHSR1) to 1-d-old mouse pups and recorded weight gain, gastric milk contents (milkbands), axillary temperature, and survival between age 1 and 10 d. The results showed a dose-related interference with all measures. These data show that (1) growth failure induced by rimonabant is generalized to another CB1 antagonist and (2) cannabinoid CB1 receptor activation by endocannabinoids is essential for normal milk ingestion and development in mice. This supports our hypothesis that endocannabinoid deficiency and perhaps CB1 receptor dysfunction represents the uncharacterized biologic vulnerability, which underlies NOFTT.     

Clinical Features and Comparison of Kingella and Non–Kingella Endocarditis in Children,Israel

Kingella spp. have emerged as an important cause of invasive pediatric diseases. Data on Kingella infective endocarditis (KIE) in children are scarce. We compared the clinical features of pediatric KIE cases with those of Streptococcus species IE (StIE) and Staphylococcus aureus IE (SaIE). A total of 60 patients were included in the study. Throughout the study period, a rise in incidence of KIE was noted. KIE patients were significantly younger than those with StIE and SaIE, were predominately boys, and had higher temperature at admission, history of oral aphthae before IE diagnosis, and higher lymphocyte count (p<0.05). Pediatric KIE exhibits unique features compared with StIE and SaIE. Therefore, in young healthy children <36 months of age, especially boys, with or without a congenital heart defect, with a recent history of oral aphthae, and experiencing signs and symptoms compatible with endocarditis, Kingella should be suspected as the causative pathogen.     

10 K: a large‐scale prospective longitudinal study in Israel

European Journal of Epidemiology - The 10&nbsp;K is a large-scale prospective longitudinal cohort and biobank that was established in Israel. The primary aims of the study include development...     

Schmorl’s nodes distribution in the human spine and its possible etiology

Although Schmorl’s nodes (SNs) are a common phenomenon in the normal adult population, their prevalence is controversial and etiology still debatable. The objective was to establish the spatial distribution of SNs along the spine in order to reveal its pathophysiology. In this study, we examined 240 human skeleton spines (T4-L5) (from the Hamann–Todd Osteological Collection) for the presence and location of SNs. To determine the exact position of SNs, each vertebral body surface was divided into 13 zones and 3 areas (anterior, middle, posterior). Our results show that SNs appeared more frequently in the T7-L1 region. The total number of SNs found in our sample was 511: 193 (37.7%) were located on the superior surface and 318 (62.3%) on the inferior surface of the vertebral body. SNs were more commonly found in the middle part of the vertebral body (63.7%). No association was found between the SNs location along the spine and gender, ethnicity and age. This study suggests that the frequency distribution of SNs varies with vertebra location and surface. The results do not lend support to the traumatic or disease explanation of the phenomenon. SNs occurrences are probably associated with the vertebra development process during early life, the nucleus pulposus pressing the weakest part of the end plate in addition to the various strains on the vertebrae and the intervertebral disc along the spine during spinal movements (especially torsional movements).     

Induction in myeloid leukemic cells of genes that are expressed in different normal tissues

Using DNA microarray and cluster analysis of expressed genes in a cloned line (M1-t-p53) of myeloid leukemic cells, we have analyzed the expression of genes that are preferentially expressed in different normal tissues. Clustering of 547 highly expressed genes in these leukemic cells showed 38 genes preferentially expressed in normal hematopoietic tissues and 122 other genes preferentially expressed in different normal nonhematopoietic tissues, including neuronal tissues, muscle, liver, and testis. We have also analyzed the genes whose expression in the leukemic cells changed after activation of WT p53 and treatment with the cytokine IL-6 or the calcium mobilizer thapsigargin. Of 620 such genes in the leukemic cells that were differentially expressed in normal tissues, clustering showed 80 genes that were preferentially expressed in hematopoietic tissues and 132 genes in different normal nonhematopoietic tissues that also included neuronal tissues, muscle, liver, and testis. Activation of p53 and treatment with IL-6 or thapsigargin induced different changes in the genes preferentially expressed in these normal tissues. These myeloid leukemic cells thus express genes that are expressed in normal nonhematopoietic tissues, and various treatments can reprogram these cells to induce other such nonhematopoietic genes. The results indicate that these leukemic cells share with normal hematopoietic stem cells the plasticity of differentiation to different cell types. It is suggested that this reprogramming to induce in malignant cells genes that are expressed in different normal tissues may be of clinical value in therapy.     

Microcoil embolisation for ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy

BACKGROUND AND AIM: Percutaneous transcatheter occlusion with ethanol injection of septal arteries is an efficient treatment procedure of hypertrophic obstructive cardiomyopathy (HOCM). The aim of our study was to evaluate the feasibility and efficiency of septal artery embolisation with microcoils. METHODS: Microcoils were delivered through the guide-wire lumen of a 2mm-diameter coaxial balloon positioned inside the target vessel as distally as possible. One or more 0.018"-straight microcoils (Hilal straight coils, Cook, USA) were used for each target vessel until complete flow obstruction was achieved. The intraventricular pressure gradient was measured before, during and after the procedure. Septal branch occlusion was finally documented by coronary angiography. RESULTS: We treated 7 patients (5 males; mean age: 48 +/- 10 years). All patients were symptomatic (NYHA class III or IV). The target vessels were successfully occluded in all patients without complications. Moderate pain was recorded during and after the procedure and the CK level increased five- to ten-fold. The pressure gradient diminished during the procedure from 72 +/- 21 mmHg to 30 +/- 15 mmHg. The number of coils delivered ranged from 3 to 7 per patient. The embolised septal branches included 1 vessel in 5 patients, 2 vessels in 1 patient and 3 vessels in 1 case. After the procedure, the pressure gradient, evaluated by transthoracic echocardiography, was 34 +/- 16 mmHg and 42 +/- 12 mmH at 3 month-follow-up. Clinical improvement was recorded in all patients after the procedure (NYHA class I or II). Temporary pacing was necessary in 3 patients during and immediately after the procedure but no patient needed permanent pacing. CONCLUSIONS: Microcoil embolisation is an efficient and safe approach for transcatheter ablation of septal hypertrophy in HOCM. This technique induced myocardial necrosis without the toxic effects of alcohol, reducing the risk of complications such as permanent pacemaker implantation or ethanol flow to other myocardial regions.