Effects of histamine H3 receptor ligands on the rewarding, stimulant and motor-impairing effects of ethanol in DBA/2J mice

Histamine H3 receptor (H3R) antagonists are currently being investigated for the possible therapeutic use in various cognitive deficits such as those in schizophrenia, attention deficit hyperactivity disorder and Alzheimer's disease. Our previous studies suggest a role for H3Rs in ethanol-related behaviors in rat and mice. Here we have examined the role of different H3R ligands on the effects of ethanol in conditioned place preference (CPP) paradigm, stimulation of locomotor activity and motor impairment in rotarod and balance beam in male DBA/2J mice. We found that H3R antagonists ciproxifan and JNJ-10181457 inhibited the ethanol-evoked CPP whereas H3R agonist immepip did not alter ethanol-induced place preference. Acute stimulatory response by ethanol was also modulated by H3R ligands. Ciproxifan increased ethanol activation when ethanol was given 1g/kg but not at 1.5g/kg dose. Immepip pretreatment diminished ethanol stimulation and increased motor-impairing effects of ethanol on the balance beam. In conclusion, these findings give further evidence of the involvement of H3R in the regulation of the effects of ethanol. The inhibition of ethanol reward by H3R antagonism implies that H3R might be a possible target to suppress compulsory ethanol seeking. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.     

Toll‐like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics

The respiratory syncytial virus (RSV) antigen serves as ligand for Toll‐like receptor (TLR) 4 that is a transmembrane signaling receptor in macrophages and dendritic cells. According to current evidence single nucleotide polymorphism involving amino acid 299 influences the susceptibility to severe RSV infections. The Asp299Gly allele has been shown to influence the TLR4‐mediated signaling causing conformational change in the extracellular domain that recognizes pathogen‐associated molecular patterns. The aim was to study the association between the TLR4 Asp299Gly polymorphism and the susceptibility to severe RSV bronchiolitis in infants. Altogether 312 cases and 356 controls, selected on the basis place of residence, date of birth, gender, and gestation at birth, were studied. When adjusted for multiple dependent variables, no allele or genotype frequency difference was found between the cases and the controls. Post hoc analysis revealed that during the year 2000 epidemics, the Gly299Gly genotype associated with protection against severe RSV and during 2004 epidemics Gly299Gly genotype and 299Gly allele associated with severe RSV. To conclude, we could not confirm the association of the Gly299 allele with severe RSV. This is consistent with the evidence that the susceptibility to severe RSV infection is principally dependent on environmental and constitutional factors. We propose that the risk of severe RSV infection may additionally depend on the interaction between individual TLR4 genotype and the particular RSV group causing bronchiolitis. Pediatr Pulmonol. 2010; 45:687–692. © 2010 Wiley‐Liss, Inc.     

“Under My Umbrella”: The housing experiences of HIV positive parents who live with and care for their children in Ontario

Positive Spaces, Healthy Places (PSHP) is the first longitudinal community-based research (CBR) initiative in Canada to examine housing stability and its relationship to health related quality of life (HRQOL) for people living with of HIV/AIDS (PHAs). As part of our mixed method data collection strategy in-depth, semi-structured interviews were conducted with 50 PHAs across Ontario to provide a deeper understanding of the impact that housing instability has on their mental and physical health. Emerging from the qualitative interviews were the unique issues and concerns that were reported by parents who live with and care for their children. These parents face dire housing, economic and social challenges that are associated with significant risks for poor health outcomes. Poor housing conditions, unsafe neighborhoods, barriers to supports for themselves and their children, HIV related stigma, discrimination, racism, and poverty have been identified by these families as being among their most pressing concerns. This results in increased stress and anxiety that has a negative impact on the mental health of HIV positive parents. In order to more effectively support HIV positive parents and their children, health and social service practices and policies must respond to the unique challenges that face these families.     

The South Karelia Air Pollution Study: Effects of Low-Level Exposure to Malodorous Sulfur Compounds on Symptoms

Exposure to very low levels of ambient-air malodorous sulfur compounds and their effect on eye irritation, respiratory-tract symptoms, and central nervous system symptoms in adults were assessed. A cross-sectional self-administered questionnaire (response rate = 77%) was distributed during March and April 1992 to adults (n = 336) who lived in a neighborhood that contained a pulp mill and in a nonpolluted reference community (n = 380). In the exposed community, the measured annual mean concentrations of total reduced sulfur compounds and sulfur dioxide measured in two stations were 2 to 3 μg/m³ and 1 μg/m³, respectively. In the reference community, the annual mean concentration of sulfur dioxide was 1 μg/m³. The residents of the community near the pulp mill reported an excess of cough, respiratory infections, and headache during the previous 4 wk, as well as during the preceding 12 mo. The relative risk for headache was increased significantly in the exposed community, compared with the reference area: the adjusted odds ratio (aOR) was 1.83 (95% confidence interval [95% CI] = 1.06–3.15] during the previous 4 wk and 1.70 (95% CI = 1.05–2.73) during the preceding 12 mo. The relative risk for cough was also increased during the preceding 12 mo (aOR = 1.64, 95% CI = 1.01–2.64). These results indicated that adverse health effects of malodorous sulfur compounds occur at lower concentrations than reported previously.     

“Why are you pregnant? What were you thinking?”: How women navigate experiences of HIV-related stigma in medical settings during pregnancy and birth

Having children is a growing reality for women living with HIV in Canada. It is imperative to understand and respond to women’s unique experiences and psychosocial challenges during pregnancy and as mothers including HIV-related stigma. This qualitative study used a narrative methodological approach to understand women’s experiences of HIV-related stigma as they navigate health services in pregnancy (n = 66) and early postpartum (n = 64). Narratives of women living with HIV expose the spaces where stigmatizing practices emerge as women seek perinatal care and support, as well as highlight the relationship between HIV-related stigma and disclosure, and the impact this has on women’s pregnancy and birthing experiences.     

Effect of intravesical instillations on the human complement factor H related protein (BTA stat) test.

OBJECTIVES: The BTA stat is a rapid, non-invasive, qualitative urine test that detects bladder tumor-associated antigen (human complement factor H related protein) in urine. The sensitivity of this test is superior to that of urine cytology in detecting primary and recurrent tumors of the urinary bladder. Intravesical instillations are widely used to avoid recurrences and even progression. The objective of this study was to evaluate the effect of intravesical treatments on the BTA stat Test. METHODS: 501 consecutive patients followed up for bladder cancer were studied, of which 490 were eligible for analysis. Three hundred and twenty-seven (66.7%) of the patients had no history of intravesical treatments, whereas the remaining 163 (33.3%) had received treatments: 66 (40.5%) at the time of evaluation. A voided urine sample was obtained prior to cystoscopy and split for culture and BTA stat testing. The overall sensitivity and specificity were calculated and compared to the patients with no, past and present instillations. RESULTS: The overall sensitivity for the BTA stat Test was 56.6%, and the specificity was 76.4%. The specificity of the BTA stat Test was 80.7, 70.7 and 65.3% in those with no, past or present intravesical instillation treatments, respectively. The difference in specificity between those with no and present instillations was significant (p = 0.023), whereas the notable difference between those with no and past instillations did not reach significance (p = 0.076), nor was the difference between patients with past and present instillations significant (p = 0.558). Present instillation of mitomycin C had the strongest adverse effect on the test as the specificity was only 25.0%, whereas past treatment did not interfere with testing. The adverse effect of BCG treatment on testing extended. CONCLUSION: The overall specificity of the test is decreased in patients receiving intravesical treatments, whereas past treatments did not interfere with testing in general. However, the adverse effect of BCG on testing seems to extend, and therefore it is suggested that the BTA stat Test should not be used in patients having received BCG, and in those with present instillation of any type.     

Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T-cell protein tyrosine phosphatase

Background  

T-cell protein tyrosine phosphatase (TCPTP/TC45) is a ubiquitously expressed intra-cellular non-receptor protein tyrosine phosphatase involved in the negative regulation of several cancer relevant cellular signalling pathways. We have previously shown that interaction between the α-cytoplasmic tail of α1β1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intra-molecular bond in TCPTP. Thus, inhibition of the regulatory interaction in TCPTP is a desirable strategy for TCPTP activation and attenuation of oncogenic RTK signalling. However, this is challenging with low molecular weight compounds.     

The South Karelia Air Pollution Study: changes in respiratory health in relation to emission reduction of malodorous sulfur compounds from pulp mills.

The authors assessed the health effects of emission reduction of malodorous sulfur compounds in a prospective cohort study with a controlled natural experiment. A total of 810 subjects (83%) participated in the follow up: 316 from the severely polluted, 306 from the moderately polluted, and 188 from the nonpolluted communities. In the severely polluted community, the annual ambient air concentration of total reduced sulfur compounds decreased from 11 microg/m3 to 6 microg/m3. Compared with the nonpolluted community, the relative decrease in acute respiratory infections, adjusted for a change in smoking habits, was 0.53 episodes/person-year (95% confidence interval = 0.22, 0.83) in the severely polluted community and 0.36 episodes/person-year (95% confidence interval = 0.06, 0.66) in the moderately polluted community. In addition, the frequency of nasal symptoms (p = .004) and cough (p = .037) decreased significantly. The results are consistent with the hypothesis that exposure to malodorous sulfur compounds increases the risk of acute respiratory infections and symptoms of the respiratory tract.