Characterization and localization of galanin receptors in human entorhinal cortex

The neuropeptide galanin (GAL) has a widespread distribution throughout the human cortex. The entorhinal cortex (ENT) plays a crucial role in the transfer of cortico-cortical information related to memory and displays severe degeneration in Alzheimer's disease (AD). However, very little is known about the pharmacology of the GAL receptor (GALR) in normal human ENT. Therefore, we pharmacologically visualized their distribution and characterized GALRs using in vitro receptor autoradiography and radioligand binding assays. Autoradiograms revealed intense GALR labeling, mainly in the substantia innominata, hypothalamus, the bed nucleus of the stria terminalis and within layers 2 and 4 of the ENT. Kinetic experiments showed that saturation of GALR sites by [125I]GAL (human) (hGAL) occurred within 2 h and that this binding readily reversed in the presence of a GTP analog, but not in the presence of excess unlabeled hGAL. Analysis of [125I]hGAL binding data from saturation experiments gave KD values of 98.6+/-21.6 pM, Bmax values of 52.9+/-32.4 fmol/mg protein and identified a high and low affinity state of the GALR. The presence of 5'-guanylylimidodiphosphate (GppNHp) or NaCl reduced the agonist labeling of hGALR in ENT membranes.     

Impact of anti-vaccine movements on pertussis control: the untold story

To assess the impact of anti-vaccine movements that targeted pertussis whole-cell vaccines, we compared pertussis incidence in countries where high coverage with diphtheria-tetanus-pertussis vaccines (DTP) was maintained (Hungary, the former East Germany, Poland, and the USA) with countries where immunisation was disrupted by anti-vaccine movements (Sweden, Japan, UK, The Russian Federation, Ireland, Italy, the former West Germany, and Australia). Pertussis incidence was 10 to 100 times lower in countries where high vaccine coverage was maintained than in countries where immunisation programs were compromised by anti-vaccine movements. Comparisons of neighbouring countries with high and low vaccine coverage further underscore the efficacy of these vaccines. Given the safety and cost-effectiveness of whole-cell pertussis vaccines, our study shows that, far from being obsolete, these vaccines continue to have an important role in global immunisation.     

PCR amplification of murine immunoglobulin germline V genes: strategies for minimization of recombination artefacts

Murine immunoglobulin germline V genes exist as multiple sequences arranged in tandem in germline DNA. Because members of V gene families are very similar, they can be amplified simultaneously using the polymerase chain reaction (PCR) with a single set of primers designed over regions of sequence similarity. In the present paper, the variables relevant to production of artefacts by recombination between different germline sequences during amplification are investigated. Pfu or Taq DNA polymerases were used to amplify from various DNA template mixtures with varying numbers of amplification cycles. Pfu generated a higher percentage of recombination artefacts than Taq. The number of artefacts and their complexity increased with the number of amplification cycles, becoming a high proportion of the total number of PCR products once the 'plateau phase' of the reaction was reached. Recombination events were located throughout the approximately 1-kb product, with no preferred sites of cross-over. By using the minimally detectable PCR bands (produced by the minimum number of amplification cycles), recombination artefacts can be virtually eliminated from PCR amplifications involving mixtures of very similar sequences. This information is relevant to all studies involving PCR amplification of members of highly homologous multigene families of cellular or viral origin.     

Intra-arterial regional anaesthesia for hand surgery with alkalinized 0.5% lignocaine

Intra-arterial regional anaesthesia (IARA) for hand surgery is an old, forgotten technique. One of the causes of low popularity may be a scalding sensation in the hand during intra-arterial injection of lignocaine, which may be caused by low pH of lignocaine's solution. In this randomized, double-blind study, normal (pH 5.2-5.3) or alkalinized (pH 7.2-7.3) preservative-free 0.5% lignocaine 1.5 mg kg-1 was injected into the radial arteries of forty adult patients to produce anaesthesia for ambulatory hand surgery. Scalding sensation in the hand during intra-arterial injection (VAS) was less pronounced with alkalinized lignocaine (P = 0.04). The time of onset and regression of analgesia was similar in both groups. Four patients in group 1 (normal lignocaine) and six patients in group 2 (alkalinized lignocaine) needed supplemental analgesia at the start of surgery (NS). Cannulation time, operating conditions, motor blockade, surgical-, and tourniquet pain scores (VAS) and patient's acceptance were similar. Three patients (two in group 1 and one in group 2) had minor systemic adverse effects after tourniquet release (NS). Nine patients in group 1 and seven in group 2 developed minor bruises after cannulation (NS). No other sequelae of intra-arterial injections were observed. We conclude that alkalinized 0.5% lignocaine was less painful on injection than normal lignocaine and should be preferred for intra-arterial anaesthesia for hand surgery.     

Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease

Over the past decade, neurotrophic factors have generated much excitement for their potential as therapy for neurological disorders. In this regard, nerve growth factor (NGF), the founding member of the neurotrophin family, has generated great interest as a potential target for the treatment of Alzheimer's disease (AD). This interest is based on the observation that cholinergic basal forebrain (CBF) neurons which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus undergo selective and severe degeneration in advanced AD and that these neurons are dependent upon NGF and its receptors for their survival. In fact, NGF transduces its effects by binding two classes of cell surface receptors, TrkA and p75(NTR), both of which are produced by CBF neurons. This review focuses on NGF/receptor binding, signal transduction, regulation of specific cellular endpoints, and the potential use of NGF in AD. Alterations in NGF ligand and receptor expression at different stages of AD are summarized. Recent results suggest that cognitive deficits in early AD and mild cognitive impairment (MCI) are not associated with a cholinergic deficit. Thus, the earliest cognitive deficits in AD may involve brain changes other than simply cholinergic system dysfunction. Recent findings indicate an early defect in NGF receptor expression in CBF neurons; therefore treatments aimed at facilitating NGF actions may prove highly beneficial in counteracting the cholinergic dysfunction found in end-stage AD and attenuating the rate of degeneration of these cholinergic neurons.     

Prolonged survival in a patient with sinonasal teratocarcinosarcoma with cranial extension. Case report

Sinonasal teratocarcinosarcoma is a rare malignant neoplasm characterized by the combined histological features of carcinosarcoma and teratoma. The primary symptoms of this tumor are usually nasal obstruction and epistaxis, and a nasal cavity mass is the most common clinical finding. The authors describe an exceptionally rare case in which the patient presented with massive intracranial extension and exhibited confusion as an initial symptom. He subsequently underwent combined radical surgery and radiation therapy and has remained free of disease for 31 months. The surgical approach to the lesion, histological features, and clinical course are detailed.