Quantitative interpretation of utterances and movements from videoed interactions between rheumatology nurses and patients commencing methotrexate: a pilot study.

Background: Educating patients about methotrexate is a core role of rheumatology nurses. We have previously reported the scoring of videoed interviews of rheumatology nurses educating patients prior to commencing methotrexate in comparison with the Calgary-Cambridge consultation model, and the qualitative analysis of the transcripts (Robinson et al. Musculoskeletal Care 2021).

An exploration of the experiences of rheumatology nurses counselling patients on methotrexate therapy.

Objectives: Methotrexate is commonly used to treat patients with inflammatory arthritis. A key role of a rheumatology nurse is to educate patients on how to take this drug safely prior to the commencement of treatment. The objective of the present study was to explore the experiences of rheumatology nurses conducting this role, focusing on the content of the consultation and training received to perform the role.

Alpha Adrenergic Induction of Transport of Lysosomal Enzyme across the Blood-Brain Barrier.

The impermeability of the adult blood-brain barrier (BBB) to lysosomal enzymes impedes the ability to treat the central nervous system manifestations of lysosomal storage diseases. Here, we found that simultaneous stimulation of the alpha1 and alpha2 adrenoreceptor restores in adult mice the high rate of transport for the lysosomal enzyme P-GUS that is seen in neonates but lost with development. Beta adrenergics, other monoamines, and acetylcholine did not restore this transport.

Rapid identification of bacterial biofilms and biofilm wound models using a multichannel nanosensor.

Identification of infectious bacteria responsible for biofilm-associated infections is challenging due to the complex and heterogeneous biofilm matrix. To address this issue and minimize the impact of heterogeneity on biofilm identification, we developed a gold nanoparticle (AuNP)-based multichannel sensor to detect and identify biofilms based on their physicochemical properties. Our results showed that the sensor can discriminate six bacterial biofilms including two composed of uropathogenic bacteria.

Functional gold nanoparticles as potent antimicrobial agents against multi-drug-resistant bacteria.

We present the use of functionalized gold nanoparticles (AuNPs) to combat multi-drug-resistant pathogenic bacteria. Tuning of the functional groups on the nanoparticle surface provided gold nanoparticles that were effective against both Gram-negative and Gram-positive uropathogens, including multi-drug-resistant pathogens. These AuNPs exhibited low toxicity to mammalian cells, and bacterial resistance was not observed after 20 generations.

The evolutionary histories of clinical and environmental SHV β-lactamases are intertwined.

The rise of antibiotic-resistant pathogens focuses our attention on the source of antibiotic resistance genes, on the existence of these genes in environments exposed to little or no antibiotics, and on the relationship between resistance genes found in the clinic and those encountered in non-clinical settings. Here, we address the evolutionary history of a class of resistance genes, the SHV β-lactamases. We focus on bla SHV genes isolated both from clinical and non-clinical sources and show that clinically important resistance determinants arise repeatedly from within a diverse pool of bla SHV genes present in the environment.

Rethinking the composition of a rational antibiotic arsenal for the 21st century.

The importance of the human microbiome in health may be the single most valuable development in our conception of the microbial world since Pasteur's germ theory of the 1860s. Its implications for our understanding of health and pathogenesis are profound. Coupled with the revolution in diagnostics that we are now witnessing - a revolution that changes medicine from a science of symptoms to a science of causes - we cannot continue to develop antibiotics as we have for the past 80 years.

Resistance is futile: the bacteriocin model for addressing the antibiotic resistance challenge.

Pathogenic bacteria resistant to many or all antibiotics already exist. With the decline in microbiological research at pharmaceutical companies, the high rate at which resistance has evolved and spread has demanded a novel approach to addressing this critical human health issue. In the present paper, we propose a new paradigm in antibiotic discovery and development, one that applies ecological and evolutionary theory to design antimicrobial drugs that are more difficult and/or more costly to resist.

Human immunodeficiency virus-1 uses the mannose-6-phosphate receptor to cross the blood-brain barrier.

HIV-1 circulates both as free virus and within immune cells, with the level of free virus being predictive of clinical course. Both forms of HIV-1 cross the blood-brain barrier (BBB) and much progress has been made in understanding the mechanisms by which infected immune cells cross the blood-brain barrier BBB. How HIV-1 as free virus crosses the BBB is less clear as brain endothelial cells are CD4 and galactosylceramide negative.

Negotiating targets with patients: choice of target in relation to occupational state.

Objectives: Following the recent National Institute for Health and Clinical Excellence guidance on the management of RA, we were interested to see if we could negotiate targets for treatment with patients in routine clinics, how they would express this and whether staying at work would be a target.

Methods: One hundred RA patients were recruited. They were consecutive within clinics, but not all clinics were used.

Impairments in brain-to-blood transport of amyloid-β and reabsorption of cerebrospinal fluid in an animal model of Alzheimer's disease are reversed by antisense directed against amyloid-β protein precursor.

The blood-brain barrier (BBB) influences brain levels of amyloid-β (Aβ) by transporting Aβ out of the brain (efflux) and by the reabsorption of cerebrospinal fluid (CSF) into the blood stream (bulk flow). In Alzheimer's disease (AD) and normal aging, unknown factors impair Aβ efflux and bulk flow in aging and in AD. These impairments have been proposed as mechanisms by which the Aβ burden in brain can increase.

Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration.

Neurosteroids hold great promise for the treatment of diseases of the central nervous system (CNS). We compared the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection. Both neurosteroids appeared in blood and brain after either method of administration, but with important differences in uptake.

Role of bacteriocins in mediating interactions of bacterial isolates taken from cystic fibrosis patients.

Pseudomonas aeruginosa (Pa) and Burkholderia cepacia complex (Bcc) lung infections are responsible for much of the mortality in cystic fibrosis (CF). However, little is known about the ecological interactions between these two, often co-infecting, species. This study provides what is believed to be the first report of the intra- and interspecies bacteriocin-like inhibition potential of Pa and Bcc strains recovered from CF patients.

Minimal penetration of lipopolysaccharide across the murine blood-brain barrier.

LPS given peripherally or into the brain induces a neuroinflammatory response. How peripheral LPS induces its effects on brain is not clear, but one mechanism is that LPS crosses the blood-brain barrier (BBB). Alternatively, LPS acts outside the BBB by stimulating afferent nerves, acting at circumventricular organs, and altering BBB permeabilities and functions.

Testing the neurovascular hypothesis of Alzheimer's disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition.

Decreased clearance is the main reason amyloid-beta protein (Abeta) is increased in the brains of patients with Alzheimer's disease (AD). The neurovascular hypothesis states that this decreased clearance is caused by impairment of low density lipoprotein receptor related protein-1 (LRP-1), the major brain-to-blood transporter of Abeta at the blood-brain barrier (BBB). As deletion of the LRP-1 gene is a lethal mutation, we tested the neurovascular hypothesis by developing a cocktail of phosphorothioate antisenses directed against LRP-1 mRNA.

Transport of prion protein across the blood-brain barrier.

The cellular form of the prion protein (PrP(c)) is necessary for the development of prion diseases and is a highly conserved protein that may play a role in neuroprotection. PrP(c) is found in both blood and cerebrospinal fluid and is likely produced by both peripheral tissues and the central nervous system (CNS). Exchange of PrP(c) between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications, but it is unknown whether PrP(c) can cross the blood-brain barrier (BBB).

Effects of triglycerides, obesity, and starvation on ghrelin transport across the blood-brain barrier.

Human ghrelin is transported across the blood-brain barrier (BBB) of normal mice. Here, we studied the effects of triglycerides, obesity, and starvation in retired breeder mice maintained on a high fat diet, mice age-matched to the retired breeders but maintained on normal chow, and 8-week-old mice maintained on breeder chow. The rate of ghrelin transport across the BBB was studied by both the intravenous administration method of multiple-time regression analysis and by the brain perfusion method.

Copper complexing decreases the ability of amyloid beta peptide to cross the BBB and enter brain parenchyma.

The amyloid hypothesis states that amyloid beta protein (Abeta) plays a major causal role in the onset of Alzheimer's disease. Toxicity of Abeta can be modified by metal ions. Two mechanisms by which such Abeta and metal ions could interact are by enhanced oxidative stress or by altered fibrillation.

Polypeptide point modifications with fatty acid and amphiphilic block copolymers for enhanced brain delivery.

There is a tremendous need to enhance delivery of therapeutic polypeptides to the brain to treat disorders of the central nervous system (CNS). The brain delivery of many polypeptides is severely restricted by the blood-brain barrier (BBB). The present study demonstrates that point modifications of a BBB-impermeable polypeptide, horseradish peroxidase (HRP), with lipophilic (stearoyl) or amphiphilic (Pluronic block copolymer) moieties considerably enhance the transport of this polypeptide across the BBB and accumulation of the polypeptide in the brain in vitro and in vivo.

Permeability of the blood-brain barrier to HIV-1 Tat.

Infection with human immunodeficiency virus-1 (HIV-1) is associated with dysfunctions of the central nervous system (CNS). HIV-1 induces its effects on the CNS by a variety of mechanisms, including by shedding the neurotoxic viral proteins such as gp120 and Tat. Both HIV-1 and gp120 have been shown to cross the blood-brain barrier (BBB).

Triglycerides induce leptin resistance at the blood-brain barrier.

Obesity is associated with leptin resistance as evidenced by hyperleptinemia. Resistance arises from impaired leptin transport across the blood-brain barrier (BBB), defects in leptin receptor signaling, and blockades in downstream neuronal circuitries. The mediator of this resistance is unknown.

Pharmacological profiles of peptide drug candidates for the treatment of Alzheimer's disease.

Amyloid plaques in brain, composed of aggregates of amyloid-beta peptide, play a central role in the pathogenesis of Alzheimer's disease and represent a good target for treatment. We have shown previously that a 5-amino acid beta-sheet breaker peptide (iA beta 5p), end-protected, has the ability to induce a dramatic reduction in amyloid deposition in two different transgenic Alzheimer's models (Permanne, B., Adessi, C.

Passage of amyloid beta protein antibody across the blood-brain barrier in a mouse model of Alzheimer's disease.

Vaccinations against amyloid beta protein (A beta P) reduce amyloid deposition and reverse learning and memory deficits in mouse models of Alzheimer's disease. This has raised the question of whether circulating antibodies, normally restricted by the blood-brain barrier (BBB), can enter the brain [Nat. Med.

Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure.

The novel hormone ghrelin is a potent orexigen that may counterbalance leptin. Ghrelin is the only secreted molecule requiring post-translational acylation with octanoic acid to ensure bioactivity. Ghrelin, predominantly derived from the stomach, may target neuroendocrine networks within the central nervous system (CNS) to regulate energy homeostasis.

Dietary nucleotides prevent decrease in cellular immunity in ground-based microgravity analog.

Microgravity and stress of spaceflights result in immune dysfunction. The role of nutrition, especially nucleotide supplementation, has become an area of intensive research and significant interest in immunomodulation for maintenance of cellular immune responses. The studies presented here evaluate the plausibility of administering nucleotides to obviate immune dysfunction in an Earth-based in vivo analog of microgravity as studied in anti-orthostatic tail suspension (AOS) of mice.