Sex differences in hyperalgesia during morphine infusion: effect of gonadectomy and estrogen treatment

Morphine treatment can paradoxically increase nociception (i.e. hyperalgesia). Since there are putative sex differences in nociception and morphine sensitivity, we compared nociception in male and female mice using the tail-withdrawal test during continuous infusion of two morphine doses (1.6 and 40.0 mg/kg/24 h). Both doses caused hyperalgesia in both sexes, but onset in females always preceded that of males. Although the larger dose initially evoked analgesia, naltrexone (NTX) pellets implanted prior to morphine infusion abolished analgesia but not hyperalgesia. Distinct sex differences also characterized each morphine dose. Specifically, the lower morphine dose caused hyperalgesia that dissipated after 6 days in males but persisted in females for a minimum of 14 days. Despite this difference, N-methyl-d-aspartate (NMDA) receptor antagonists reversed hyperalgesia in both sexes. In contrast, the higher morphine dose evoked hyperalgesia that resolved concurrently in both sexes, but hyperalgesia was reversed by NMDA receptor antagonists in males only. Ovariectomy (OVX), but not OVX followed by estrogen treatment, abolished both sex differences, and resulted in females exhibiting the male-typical pattern. This study thus demonstrates NTX-insensitive morphine hyperalgesia in females as previously reported for males. However, females utilized hyperalgesic mechanisms which were distinct from those employed by males. Data from females subject to OVX/estrogen replacement further indicate that females possess functional male-typical hyperalgesic mechanisms, but are diverted from their use by ovarian sex steroids. Finally, the finding that each morphine infusion dose was characterized by a unique sex difference provides additional evidence for distinct multiple hyperalgesic systems.     

Health disparities and culturally specific treatment: perspectives and expectancies of African American smokers

Researchers suggest that culturally specific (CS) interventions are important in addressing smoking-related health disparities. Yet, little research has examined the perspectives of African American smokers regarding these efforts. This qualitative study sought to gain insight into perceptions related to (a) the smoking prevalence among African Americans, (b) smoking-related health disparities, (c) expectancies for CS interventions, (d) methods of recruiting research participants, and (e) key intervention components. Six focus groups were conducted with 41 African American smokers (aged 21-64) at a community health center. Content analyses revealed several themes, including the perception that smoking is normative among African Americans, limited knowledge of racial health disparities, mixed perceptions regarding race as a risk factor for illness, and mixed expectancies for the efficacy of CS interventions. In conclusion, individual differences, such as smoking norms, knowledge of health disparities, and intervention expectations may influence receptivity to CS treatments. Implications for tobacco interventions among African Americans are discussed.     

Targeting ECM-integrin interaction with liposome-encapsulated small interfering RNAs inhibits the growth of human prostate cancer in a bone xenograft imaging model.

The intricate intracellular communication between stromal and epithelial cells, which involves cell-cell-, cell-insoluble extracellular matrix- (ECM), and cell-soluble factor-mediated signaling processes, is an attractive target for therapeutic intervention in hormone-refractory and bone-metastatic prostate cancer. In the present study we demonstrated that androgen-independent PC3 prostate cancer cells adhered to and migrated on vitronectin (VN), a major noncollagenous ECM in mature bone, through the expression of alphav-containing integrin receptors alphavbeta1 and alphavbeta5 on the cell surface, as determined by antibody function blocking assay and flow cytometry analysis. Small interfering RNAs (siRNAs) targeting human integrin alphav markedly reduced their respective mRNA and protein expression in cells, resulting in nearly complete reduction in VN-mediated cancer progression in vitro. In vivo quantitative bioluminescence analysis of human prostate cancer bone xenografts demonstrated for the first time that intratumoral administration of liposome-encapsulated human alphav-siRNAs significantly inhibits the growth of luciferase-tagged PC3 tumors in skeleton, which was associated with decreased integrin alphav expression and increased apoptosis in tumor cells. This integrin-based gene therapy is particularly suitable for the treatment of prostate cancer bone metastasis.     

Optometry Australia's chairside reference for the diagnosis and management of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in people over the age of 50 years in Australia. Optometry Australia has developed this AMD chairside reference in consultation with a member-based working group comprised of experienced practitioners. It provides an evidence-based approach to current best practice in the diagnosis and management of AMD. Optometrists should be competent in assessing patients with or at risk of developing AMD, so that they are able to provide evidence-based management including appropriate communication, diagnosis and referral when indicated. This AMD chairside reference covers risk factors for the development of AMD or progression to late-stage AMD; the current clinical classification of AMD; common signs and symptoms; optometric assessment including ocular imaging and biomarkers; differential diagnoses; and management of early, intermediate and late AMD. Optometry Australia's chairside reference is intended as a general guide for optometrists, and is not a formal management protocol.