Toxocara canis and lead alter consummatory behavior in mice

Ingestion of palatable and unpalatable solutions was measured in adult mice to which had been administered the common parasite of the dog, Toxocara canis alone, or in combination with lead. In addition, response to hot plate and susceptibility to electroconvulsive seizure were also measured. Results from the palatability test indicated that either lead or Toxocara may alter the mouse's mode of interacting with its environment. However, the two agents in combination interacted in their effects on consummatory behavior. Results from the hot plate and ECS measures were less clear with respect to how lead and/or Toxocara influence temperature reactivity and seizure susceptibility. Histological examination of the CNS in parasite infected animals revealed Wallerian Type degeneration of fiber pathways including the corpus callosum, olfactory tract, and cerebellar penduncles.     

Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition

Mitochondria are involved directly in cell survival and death. The assumption has been made that drugs that protect mitochondrial viability and prevent apoptotic cascade-induced mitochondrial permeability transition pore (MPTp) opening will be cytoprotective. Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO) B inhibitor anti-Parkinson drug. Unlike selegiline, it is not derived from amphetamine, and is not metabolized to neurotoxic L-methamphetamine derivative. In addition, it does not have sympathomimetic activity. Rasagiline is effective as monotherapy or adjunct to levodopa for patients with early and late Parkinson's disease (PD) and adverse events do not occur with greater frequency in subjects receiving rasagiline than in those on placebo. Phase III controlled studies indicate that it might have a disease-modifying effect in PD that may be related to its neuroprotective activity. Its S isomer, TVP1022, is more than 1,000 times less potent as an MAO inhibitor. Both drugs, however, have neuroprotective activity in neuronal cell cultures in response to various neurotoxins, and in vivo in response to global ischemia, neurotrauma, head injury, anoxia, etc., indicating that MAO inhibition is not a prerequisite for neuroprotection. Their neuroprotective effect has been demonstrated to be associated directly with the propargylamine moiety, which protects mitochondrial viability and MTPp by activating Bcl-2 and protein kinase C (PKC) and by downregulating the proapoptotic FAS and Bax protein families. Rasagiline and its derivatives also process amyloid precursor protein (APP) to the neuroprotective, neurotrophic, soluble APP alpha (sAPPalpha) by PKC- and MAP kinase-dependent activation of alpha-secretase. The identification of the propargylamine moiety as the neuroprotective component of rasagiline has led us to development of novel bifunctional anti-Alzheimer drugs (ladostigil) possessing cholinesterase and brain-selective MAO inhibitory activity and a similar neuroprotective mechanism of action.     

Myocardial bridging: noninvasive diagnosis with multidetector CT

An epicardial segment of a coronary artery that courses through the myocardium is termed "myocardial bridging". Generally, this is a benign condition but it may lead to angina, ischemia or infarction. The current diagnostic standard of reference is coronary catheter angiography. Intravascular ultrasound (IVUS) and intracoronary Doppler (ICD) have been recently introduced as well. These are all invasive imaging modalities. We describe the utilization of gated multidetector CT (MDCT) as a non-invasive alternative for diagnosis of this anomaly. Information regarding the tunneled coronary artery including its length, depth, precise location and surrounding myocardium is easily obtainable.     

Tolerability and immunogenicity of an eleven valent mixed carrier Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid or tetanus protein conjugate vaccine in Finnish and Israeli infants

BACKGROUND: To have wide global coverage of pneumococcal serotypes, the number of serotypes covered by the current 7-valent pneumococcal conjugate vaccine must be increased. We have studied the safety and immunogenicity of an 11-valent mixed carrier vaccine (PncDT11) in infants. METHODS: The study vaccine contained polysaccharide antigens of serotypes 1, 4, 5, 7F, 9V, 19F and 23F conjugated to tetanus protein and serotypes 3, 6B, 14 and 18C conjugated to diphtheria toxoid. The vaccine was administered to Finnish (n = 117) and Israeli (n = 135) infants at ages 2, 4, 6 and 12 months concomitantly with other vaccines used in national vaccination programs. IgG antibodies to polysaccharides were determined by enzyme immunoassay from serum samples taken at ages 2, 7, 12 and 13 months. After each injection the infants were followed for 30 min to detect any immediate adverse reactions, and parents were given a diary card to report any adverse events during the next 5 days. RESULTS: No severe adverse reactions occurred, and immediate adverse reactions were rare. After each dose approximately 30% of the vaccinees experienced local reactions of which pain was the most common. Fever of >38 degrees C was reported in 33 to 53% of the vaccinees and high fever (>40 degrees C) was reported 6 times. The PncDT11 vaccine was immunogenic. The antibody concentrations after primary immunization series were higher in Israeli than in Finnish infants, but the differences were not significant for most serotypes. The difference was most marked at 13 months, a time point at which the difference was significant in 10 of 11 serotypes. CONCLUSION: PncDT11 is safe and immunogenic in infants. The use of 11-valent pneumococcal vaccine would increase the serotype coverage beyond the currently available 7-valent vaccine.     

Treatment of pediatric intracranial arteriovenous malformations with linear-accelerator-based stereotactic radiosurgery: the University of Pennsylvania experience

There are relatively few reports detailing the outcome of children and adolescents with arteriovenous malformations (AVMs) treated with stereotactic radiosurgery (SRS). We reviewed our experience over the past decade to determine whether the outcomes and toxicity were similar to those reported in adults. Seventeen patients 18 years of age or younger underwent linear-accelerator-based SRS. The targeted volume was greater than 3 cm(3) in 65% of cases (range 0.7-25 cm(3); median volume 6.9 cm(3)). The prescribed radiation doses varied from 16 to 18 Gy, with 70% receiving the highest dose. Using only angiographic data, the obliteration rate was 80% (8 of 10 patients), but using both MRA/MRI and angiographic data, it was 53% (9 of 17 patients). Four patients developed late effects potentially attributable to the radiation between 2 months and 3 years following SRS. One of these was transient and disappeared completely within a few days, but in the other 3 patients, the neurologic sequelae were permanent. Two of the 4 complications appeared to be due to radiation necrosis/edema, whereas the remaining 2 may have been due to vasculopathy. All 4 patients with complications had treatment volumes greater than 5 cm(3) (5.4, 6.9, 11.1, 16.4 cm(3)), all had a prescribed dose of 18 Gy and all had initially presented with an AVM hemorrhage. Linear-accelerator-based SRS is effective in obliterating most AVMs in children; however, the potential for late effects exists, especially for those patients with larger target volumes.     

New supplements to infant formulas

Foods, which, in addition to their nutritional attributes, contain also elements that are considered to be health-promoting, have been termed "functional foods". In this regard, human milk has gained recognition as being the ultimate functional food for infants - by its biological compatibility, nutritional value and the undisputed added value of its health promoting qualities. Intensive research activity has recently evolved in a quest to identify and define the components of human milk that might confer disease-preventing and health-enhancing properties and to determine the instances and clinical conditions in which these factors become particularly important. The outcome of such research would also provide a rationale for advocating the supplementation of commercial infant formulas with such substances. In effect, the body of data accumulated from scientific and clinical studies on nucleotides, probiotics, prebiotics and long-chain polyunsaturated fatty acids in human milk and as additives to infant formula, has become regarded as convincing enough by the infant formula industry so as to launch into the market formulas supplemented with one or more of these factors - in an effort to emulate human milk and its beneficial effects. The following review is intended for the reader to obtain a general idea of the new supplements that have been introduced to infant formulas. We summarize the pertinent experimental and clinical observations concerning each of the supplements, pointing out their potential specific benefits, their possible disadvantages and the issues that still remain unresolved.     

Changing social gradients in cigarette smoking and cessation over two decades of adult follow-up in a British birth cohort

BACKGROUND: We aimed to establish whether socioeconomic gradients in smoking among men and women increase with age as a result of differential uptake, quitting and smoking persistence over time. METHODS: A prospective British birth cohort (all births 3-9 March 1958) was followed to 41 years. Analyses of smoking at 41 years by socioeconomic position of origin include 10,521 participants and for socioeconomic position at 23 years n = 9240. RESULTS: By 41 years half of the cohort had smoked regularly (> or = 1 cigarette/day). Smoking prevalence peaked at 23 years (40 per cent) and subsequently declined; quitting increased between 23 years (10 per cent) and 41 years (29 per cent). Individuals from manual backgrounds were more likely to smoke and less likely to quit than those from non-manual groups, and these differences increased over the two decades during which the cohort was followed up. For social position of origin, the odds ratio for current smoking at 23 years among women was 1.28 (95 per cent confidence interval (CI) 1.21, 1.35), i.e. a 28 per cent greater risk of smoking per unit increment on a four-point scale from professional/managerial to unskilled manual. The odds ratio increased to 1.45 (95 per cent CI 1.36, 1.56) at 41 years, trend over time p = 0.01. For men, equivalent results are 1.18 (1.11, 1.24) at 23 years and 1.33 (1.24, 1.42) at 41 years, trend p = 0.01. The social gradients in current smoking also increase over time for men and women using social position at 23 years. CONCLUSION: Conclusions Social gradients in smoking have become more marked across the lifecourse of this birth cohort. This implies continued socioeconomic inequalities in future health outcomes in a contemporary adult population.