The Association between Hypertension and Depression and Anxiety Disorders: Results from a Nationally-Representative Sample of South African Adults

OBJECTIVE:Growing evidence suggests high levels of comorbidity between hypertension and mental illness but there are few data from low- and middle-income countries. We examined the association between hypertension and depression and anxiety in South Africa. METHODS:Data come from a nationally-representative survey of adults (n = 4351). The Composite International Diagnostic Interview was used to measure DSM-IV mental disorders during the previous 12-months. The relationships between self-reported hypertension and anxiety disorders, depressive disorders and comorbid anxiety-depression were assessed after adjustment for participant characteristics including experience of trauma and other chronic physical conditions. RESULTS:Overall 16.7% reported a previous medical diagnosis of hypertension, and 8.1% and 4.9% were found to have a 12-month anxiety or depressive disorder, respectively. In adjusted analyses, hypertension diagnosis was associated with 12-month anxiety disorders [Odds ratio (OR) = 1.55, 95% Confidence interval (CI) = 1.10-2.18] but not 12-month depressive disorders or 12-month comorbid anxiety-depression. Hypertension in the absence of other chronic physical conditions was not associated with any of the 12-month mental health outcomes (p-values all <0.05), while being diagnosed with both hypertension and another chronic physical condition were associated with 12-month anxiety disorders (OR = 2.25, 95% CI = 1.46-3.45), but not 12-month depressive disorders or comorbid anxiety-depression. CONCLUSIONS:These are the first population-based estimates to demonstrate an association between hypertension and mental disorders in sub-Saharan Africa. Further investigation is needed into role of traumatic life events in the aetiology of hypertension as well as the temporality of the association between hypertension and mental disorders

Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer

PTEN, a phosphoinositide-3-phosphatase, serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism. Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation, especially reactive carbonyl species, which are commonly occurring by-products of arachidonic acid peroxidation. Using MCF7 and HEK-293 cells, we report that several reactive aldehydes and ketones, e.g. electrophilic α,β-enals (acrolein, 4-hydroxy-2-nonenal) and α,β-enones (prostaglandin A2, Δ12-prostaglandin J2 and 15-deoxy-Δ-12,14-prostaglandin J2) covalently modify and inactivate cellular PTEN, with ensuing activation of PKB/Akt kinase; phosphorylation of Akt substrates; increased cell proliferation; and increased nuclear β-catenin signaling. Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation, oxidative stress, or aging

BAC constructs in transgenic reporter mouse lines control efficient and specific LacZ expression in hypertrophic chondrocytes under the complete Col10a1 promoter

During endochondral ossification hypertrophic chondrocytes in the growth plate of fetal long bones, ribs and vertebrae play a key role in preparing growth plate cartilage for replacement by bone. In order to establish a reporter gene mouse to facilitate functional analysis of genes expressed in hypertrophic chondrocytes in this process, Col10a1- BAC reporter gene mouse lines were established expressing LacZ specifically in hypertrophic cartilage under the control of the complete Col10a1 gene. For this purpose, a bacterial artificial chromosome (BAC RP23-192A7) containing the entire murine Col10a1 gene together with 200 kb flanking sequences was modified by inserting a LacZ-Neo cassette into the second exon of Col10a1 by homologous recombination in E. coli. Transgenic mice containing between one and seven transgene copies were generated by injection of the purified BAC-Col10a1- lLacZ DNA. X-gal staining of newborns and embryos revealed strong and robust LacZ activity exclusively in hypertrophic cartilage of the fetal and neonatal skeleton of the transgenic offspring. This indicates that expression of the reporter gene in its proper genomic context in the BAC Col10a1 environment is independent of the integration site and reflects authentic Col10a1 expression in vivo. The Col10a1 specific BAC recombination vector described here will enable the specific analysis of effector gene functions in hypertrophic cartilage during skeletal development, endochondral ossification, and fracture callus healing