Treatment resistant trigeminal neuralgia relieved with oral sumatriptan: a case report

© 2009 Moran and Neligan; licensee Cases Network Ltd

Using vital statistics to estimate the population-level impact of osteoporotic fractures on mortality based on death certificates, with an application to France (2000-2004)

Abstract Background We developed a methodology using vital statistics to estimate the impact of osteoporotic fractures on the mortality of an entire population, and applied it to France for the period 2000-2004. Methods Current definitions of osteoporotic fractures were reviewed and their components identified. We used the International Classification of Diseases with national vital statistics data for the French adult population and performed cross-classifications between various components: age, sex, I-code (site) and E-code (mechanism of fracture). This methodology allowed identification of appropriate thresholds and categorization for each pertinent component. Results 2,625,743 death certificates were analyzed, 2.2% of which carried a mention of fracture. Hip fractures represented 55% of all deaths from fracture. Both sexes showed a similar pattern of mortality rates for all fracture sites, the rate increased with age from the age of 70 years. The E-high-energy code (present in 12% of death certificates with fractures) was found to be useful to rule-out non-osteoporotic fractures, and to correct the overestimation of mortality rates. Using this methodology, the crude number of deaths associated with fractures was estimated to be 57,753 and the number associated with osteoporotic fractures 46,849 (1.85% and 1.78% of all deaths, respectively). Conclusion Osteoporotic fractures have a significant impact on overall population mortality.</p

[11C]CHIBA-1001 as a Novel PET Ligand for α7 Nicotinic Receptors in the Brain: A PET Study in Conscious Monkeys

BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable positron emission tomography (PET) radioligands for imaging alpha7 nAChRs in the intact human brain. Here we report the novel PET radioligand [11C]CHIBA-1001 for in vivo imaging of alpha7 nAChRs in the non-human primate brain. METHODOLOGY/PRINCIPAL FINDINGS: A receptor binding assay showed that CHIBA-1001 was a highly selective ligand at alpha7 nAChRs. Using conscious monkeys, we found that the distribution of radioactivity in the monkey brain after intravenous administration of [11C]CHIBA-1001 was consistent with the regional distribution of alpha7 nAChRs in the monkey brain. The distribution of radioactivity in the brain regions after intravenous administration of [11C]CHIBA-1001 was blocked by pretreatment with the selective alpha7 nAChR agonist SSR180711 (5.0 mg/kg). However, the distribution of [11C]CHIBA-1001 was not altered by pretreatment with the selective alpha4beta2 nAChR agonist A85380 (1.0 mg/kg). Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days); which is a non-human primate model of schizophrenia. CONCLUSIONS/SIGNIFICANCE: The present findings suggest that [11C]CHIBA-1001 could be a novel useful PET ligand for in vivo study of the receptor occupancy and pathophysiology of alpha7 nAChRs in the intact brain of patients with neuropsychiatric diseases such as schizophrenia and Alzheimer's disease

DNA Adenine Methylation Is Required to Replicate Both Vibrio cholerae Chromosomes Once per Cell Cycle

DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated) sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII) of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

The role of war in deep transitions: exploring mechanisms, imprints and rules in sociotechnical systems

This paper explores in what ways the two world wars influenced the development of sociotechnical systems underpinning the culmination of the first deep transition. The role of war is an underexplored aspect in both the Techno-Economic Paradigms (TEP) approach and the Multi-level perspective (MLP) which form the two key conceptual building blocks of the Deep Transitions (DT) framework. Thus, we develop a conceptual approach tailored to this particular topic which integrates accounts of total war and mechanisms of war from historical studies and imprinting from organisational studies with the DT framework’s attention towards rules and meta-rules. We explore in what ways the three sociotechnical systems of energy, food, and transport were affected by the emergence of new demand pressures and logistical challenges during conditions of total war; how war impacted the directionality of sociotechnical systems; the extent to which new national and international policy capacities emerged during wartime in the energy, food, and transport systems; and the extent to which these systems were influenced by cooperation and shared sacrifice under wartime conditions. We then explore what lasting changes were influenced by the two wars in the energy, food, and transport systems across the transatlantic zone. This paper seeks to open up a hitherto neglected area in analysis on sociotechnical transitions and we discuss the importance of further research that is attentive towards entanglements of warfare and the military particularly in the field of sustainability transitions

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease