Recombinant Mouse PAP Has pH-Dependent Ectonucleotidase Activity and Acts through A1-Adenosine Receptors to Mediate Antinociception

Prostatic acid phosphatase (PAP) is expressed in nociceptive neurons and functions as an ectonucleotidase. When injected intraspinally, the secretory isoforms of human and bovine PAP protein have potent and long-lasting antinociceptive effects that are dependent on A1-adenosine receptor (A1R) activation. In this study, we purified the secretory isoform of mouse (m)PAP using the baculovirus expression system to determine if recombinant mPAP also had antinociceptive properties. We found that mPAP dephosphorylated AMP, and to a much lesser extent, ADP at neutral pH (pH 7.0). In contrast, mPAP dephosphorylated all purine nucleotides (AMP, ADP, ATP) at an acidic pH (pH 5.6). The transmembrane isoform of mPAP had similar pH-dependent ectonucleotidase activity. A single intraspinal injection of mPAP protein had long-lasting (three day) antinociceptive properties, including antihyperalgesic and antiallodynic effects in the Complete Freund's Adjuvant (CFA) inflammatory pain model. These antinociceptive effects were transiently blocked by the A1R antagonist 8-cyclopentyl-1, 3-dipropylxanthine (CPX), suggesting mPAP dephosphorylates nucleotides to adenosine to mediate antinociception just like human and bovine PAP. Our studies indicate that PAP has species-conserved antinociceptive effects and has pH-dependent ectonucleotidase activity. The ability to metabolize nucleotides in a pH-dependent manner could be relevant to conditions like inflammation where tissue acidosis and nucleotide release occur. Lastly, our studies demonstrate that recombinant PAP protein can be used to treat chronic pain in animal models

Hispanic health in the USA: a scoping review of the literature

Hispanics are the largest minority group in the USA. They contribute to the economy, cultural diversity, and health of the nation. Assessing their health status and health needs is key to inform health policy formulation and program implementation. To this end, we conducted a scoping review of the literature and national statistics on Hispanic health in the USA using a modified social-ecological framework that includes social determinants of health, health disparities, risk factors, and health services, as they shape the leading causes of morbidity and mortality. These social, environmental, and biological forces have modified the epidemiologic profile of Hispanics in the USA, with cancer being the leading cause of mortality, followed by cardiovascular diseases and unintentional injuries. Implementation of the Affordable Care Act has resulted in improved access to health services for Hispanics, but challenges remain due to limited cultural sensitivity, health literacy, and a shortage of Hispanic health care providers. Acculturation barriers and underinsured or uninsured status remain as major obstacles to health care access. Advantageous health outcomes from the “Hispanic Mortality Paradox” and the “Latina Birth Outcomes Paradox” persist, but health gains may be offset in the future by increasing rates of obesity and diabetes. Recommendations focus on the adoption of the Health in All Policies framework, expanding access to health care, developing cultural sensitivity in the health care workforce, and generating and disseminating research findings on Hispanic health

GAD1 is a biomarker for benign and malignant prostatic tissue

Objective. Tissue-specific markers are useful for identification of tumour type in advanced cancers of unknown origin. This study investigated the expression of glutamate decarboxylase 1 (GAD1) in prostate and control tissue compared with the established prostate-specific markers prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). Material and methods. A tissue microarray was constructed of 36 prostate adenocarcinomas, eight benign prostate samples and benign and malignant control tissues from urinary bladder, lung and rectum. Immunohistochemistry for GAD 1, PSA and PSMA was performed. The products of staining intensity and extent were analysed. The GAD1 antibody was validated by Western blot. Real-time polymerase chain reaction (RT-PCR) was performed on malignant and benign samples from each tissue type. Results. GAD 1 and PSA immunostains were significantly stronger in malignant and benign prostatic tissue than in controls. PSMA was stronger in prostate cancer than in urothelial and rectal cancer but had a lower specificity than GAD1 and PSA. GAD I expression decreased with increasing Gleason score. RT-PCR confirmed the presence of mRNA for GAD I, PSA and PSMA in prostate samples. Conclusion. GAD1 is expressed in benign and malignant prostatic tissue and may serve as a highly prostate-specific tissue biomarker.</p

Prostatic acid phosphatase, a neglected ectonucleotidase

Two recent papers reveal that the soluble and secreted prostatic acid phosphatase, an enzyme that has long served as a diagnostic marker for prostate cancer, has a membrane-bound splice variant. This enzyme exhibits ecto-5′-nucleotidase activity, is widely distributed, and implicated in the formation of chronic pain. While prostatic acid phosphatase hydrolyzes phosphomonoesters other than 5′-nucleoside monophosphates these novel data suggest that, in addition to ecto-5′-nucleotidase and the alkaline phosphatases, prostatic acid phosphatase must be taken into account in future studies on extracellular adenosine production

Health Disparities Among Mexican American Women Aged 15–44 Years: National Health and Nutrition Examination Survey, 1999–2004

Objectives. We analyzed the health of Mexican American women aged 15 to 44 years, by generation and language preference, to guide planning for reproductive health services in this growing population

Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy.

Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men

Transl Psychiatry

This study aims at assessing the burden of rare (minor allele frequency < 1%) predicted damaging variants in the whole exome of 92 bipolar I disorder (BD) patients and 1051 controls of French ancestry. Patients exhibiting an extreme phenotype (earlier onset and family history of mood disorder) were preferentially included to increase the power to detect an association. A collapsing strategy was used to test the overall burden of rare variants in cases versus controls at the gene level. Only protein-truncating and predicted damaging missense variants were included in the analysis. Thirteen genes exhibited p values exceeding 10(-3) and could be considered as potential risk factors for BD. Furthermore, the validity of the association was supported when the Exome Aggregation Consortium database non-Finnish European population was used as controls for eight of them. Their gene products are involved in various cerebral processes, some of which were previously implicated in BD and belong to pathways implicated in the therapeutic effect of lithium, the main mood stabilizer. However, exome-wide threshold for association study was not reached, emphasizing that larger samples are needed