Adiponectin: Serum-saliva associations and relations with oral and systemic markers of inflammation

This study addresses gaps in our understanding about the validity and utility of using salivary adiponectin to index serum adiponectin levels. Matched blood and saliva samples were collected on a single occasion from healthy adults (n=99; age 18–36 years, 53% male). Serum and saliva was assayed for adiponectin and inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα), and saliva was also assayed for markers of blood contamination (transferrin), total protein (salivary flow rate) and matrix metalloproteinase-8 (MMP-8). We examined the extent to which salivary adiponectin was associated with serum adiponectin, and the influence of potential confounders on the serum-saliva correlation, including age, sex, body mass index, and markers of inflammation, oral health, salivary blood contamination, and flow rate. Findings revealed a modest serum-saliva association for adiponectin, and strong positive associations between salivary adiponectin and salivary levels of inflammatory cytokines, MMP-8, transferrin, and total protein. By contrast, salivary adiponectin was not related to serum levels of inflammatory activity. The magnitude of the serum-saliva association was strengthened when controlling for total protein in saliva, blood leakage into oral fluid, salivary inflammatory cytokines, and MMP-8. The pattern of findings extends our understanding of salivary adiponectin and its potential use as an index of circulating adiponectin levels

Alzheimer's disease: new diagnostic and therapeutic tools

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lectures of M. Racchi on History and future perspectives of Alzheimer Biomarkers and of G. Scapagnini on Cellular Stress Response and Brain Ageing are summarized. Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease, which in Western society mainly accounts for clinica dementia. AD prevention is an important goal of ongoing research. Two objectives must be accomplished to make prevention feasible: i) individuals at high risk of AD need to be identified before the earliest symptoms become evident, by which time extensive neurodegeneration has already occurred and intervention to prevent the disease is likely to be less successful and ii) safe and effective interventions need to be developed that lead to a decrease in expression of this pathology. On the whole, data here reviewed strongly suggest that the measurement of conformationally altered p53 in blood cells has a high ability to discriminate AD cases from normal ageing, Parkinson's disease and other dementias. On the other hand, available data on the involvement of curcumin in restoring cellular homeostasis and rebalancing redox equilibrium, suggest that curcumin might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation, such as AD

The Na(+)/Ca(2+) exchanger NCKX4 governs termination and adaptation of the mammalian olfactory response

Sensory perception requires accurate encoding of stimulus information by sensory receptor cells. We identified NCKX4, a potassium-dependent Na(+)/Ca(2+) exchanger, as being necessary for rapid response termination and proper adaptation of vertebrate olfactory sensory neurons (OSNs). Nckx4(-/-) (also known as Slc24a4) mouse OSNs displayed substantially prolonged responses and stronger adaptation. Single-cell electrophysiological analyses revealed that the majority of Na(+)-dependent Ca(2+) exchange in OSNs relevant to sensory transduction is a result of NCKX4 and that Nckx4(-/-) mouse OSNs are deficient in encoding action potentials on repeated stimulation. Olfactory-specific Nckx4(-/-) mice had lower body weights and a reduced ability to locate an odorous source. These results establish the role of NCKX4 in shaping olfactory responses and suggest that rapid response termination and proper adaptation of peripheral sensory receptor cells tune the sensory system for optimal perception

Biologic Phenotyping of the Human Small Airway Epithelial Response to Cigarette Smoking

BACKGROUND: The first changes associated with smoking are in the small airway epithelium (SAE). Given that smoking alters SAE gene expression, but only a fraction of smokers develop chronic obstructive pulmonary disease (COPD), we hypothesized that assessment of SAE genome-wide gene expression would permit biologic phenotyping of the smoking response, and that a subset of healthy smokers would have a "COPD-like" SAE transcriptome. METHODOLOGY/PRINCIPAL FINDINGS: SAE (10th-12th generation) was obtained via bronchoscopy of healthy nonsmokers, healthy smokers and COPD smokers and microarray analysis was used to identify differentially expressed genes. Individual responsiveness to smoking was quantified with an index representing the % of smoking-responsive genes abnormally expressed (I(SAE)), with healthy smokers grouped into "high" and "low" responders based on the proportion of smoking-responsive genes up- or down-regulated in each smoker. Smokers demonstrated significant variability in SAE transcriptome with I(SAE) ranging from 2.9 to 51.5%. While the SAE transcriptome of "low" responder healthy smokers differed from both "high" responders and smokers with COPD, the transcriptome of the "high" responder healthy smokers was indistinguishable from COPD smokers. CONCLUSION/SIGNIFICANCE: The SAE transcriptome can be used to classify clinically healthy smokers into subgroups with lesser and greater responses to cigarette smoking, even though these subgroups are indistinguishable by clinical criteria. This identifies a group of smokers with a "COPD-like" SAE transcriptome

Does Respondent Driven Sampling Alter the Social Network Composition and Health-Seeking Behaviors of Illicit Drug Users Followed Prospectively?

Respondent driven sampling (RDS) was originally developed to sample and provide peer education to injection drug users at risk for HIV. Based on the premise that drug users' social networks were maintained through sharing rituals, this peer-driven approach to disseminate educational information and reduce risk behaviors capitalizes and expands upon the norms that sustain these relationships. Compared with traditional outreach interventions, peer-driven interventions produce greater reductions in HIV risk behaviors and adoption of safer behaviors over time, however, control and intervention groups are not similarly recruited. As peer-recruitment may alter risk networks and individual risk behaviors over time, such comparison studies are unable to isolate the effect of a peer-delivered intervention. This analysis examines whether RDS recruitment (without an intervention) is associated with changes in health-seeking behaviors and network composition over 6 months. New York City drug users (N = 618) were recruited using targeted street outreach (TSO) and RDS (2006–2009). 329 non-injectors (RDS = 237; TSO = 92) completed baseline and 6-month surveys ascertaining demographic, drug use, and network characteristics. Chi-square and t-tests compared RDS- and TSO-recruited participants on changes in HIV testing and drug treatment utilization and in the proportion of drug using, sex, incarcerated and social support networks over the follow-up period. The sample was 66% male, 24% Hispanic, 69% black, 62% homeless, and the median age was 35. At baseline, the median network size was 3, 86% used crack, 70% used cocaine, 40% used heroin, and in the past 6 months 72% were tested for HIV and 46% were enrolled in drug treatment. There were no significant differences by recruitment strategy with respect to changes in health-seeking behaviors or network composition over 6 months. These findings suggest no association between RDS recruitment and changes in network composition or HIV risk, which supports prior findings from prospective HIV behavioral surveillance and intervention studies

Emergence of linguistic laws in human voice

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Salt restriction in kidney disease—a missed therapeutic opportunity?

The importance of salt restriction in the treatment of patients with renal disease has remained highly controversial. In the following we marshal the current evidence that salt plays a definite role in the genesis of hypertension and target organ damage, point to practical problems of salt restriction, and report on novel pathomechanisms of how salt affects blood pressure and causes target organ damage

Application of microarray technology in pulmonary diseases

Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives

Illumination of Parainfluenza Virus Infection and Transmission in Living Animals Reveals a Tissue-Specific Dichotomy

The parainfluenza viruses (PIVs) are highly contagious respiratory paramyxoviruses and a leading cause of lower respiratory tract (LRT) disease. Since no vaccines or antivirals exist, non-pharmaceutical interventions are the only means of control for these pathogens. Here we used bioluminescence imaging to visualize the spatial and temporal progression of murine PIV1 (Sendai virus) infection in living mice after intranasal inoculation or exposure by contact. A non-attenuated luciferase reporter virus (rSeV-luc(M-F*)) that expressed high levels of luciferase yet was phenotypically similar to wild-type Sendai virus in vitro and in vivo was generated to allow visualization. After direct intranasal inoculation, we unexpectedly observed that the upper respiratory tract (URT) and trachea supported robust infection under conditions that result in little infection or pathology in the lungs including a low inoculum of virus, an attenuated virus, and strains of mice genetically resistant to lung infection. The high permissivity of the URT and trachea to infection resulted in 100% transmission to naïve contact recipients, even after low-dose (70 PFU) inoculation of genetically resistant BALB/c donor mice. The timing of transmission was consistent with the timing of high viral titers in the URT and trachea of donor animals but was independent of the levels of infection in the lungs of donors. The data therefore reveals a disconnect between transmissibility, which is associated with infection in the URT, and pathogenesis, which arises from infection in the lungs and the immune response. Natural infection after transmission was universally robust in the URT and trachea yet limited in the lungs, inducing protective immunity without weight loss even in genetically susceptible 129/SvJ mice. Overall, these results reveal a dichotomy between PIV infection in the URT and trachea versus the lungs and define a new model for studies of pathogenesis, development of live virus vaccines, and testing of antiviral therapies