Kidney dysfunction and hypertension: Role for cadmium, P450 and heme oxygenases?

Cadmium (Cd) is a metal toxin of continuing worldwide concern. Daily intake of Cd, albeit in small quantities, is associated with a number of adverse health effects which are attributable to distinct pathological changes in a variety of tissues and organs. In the present review, we focus on its renal tubular effects in people who have been exposed environmentally to Cd at levels below the provisional tolerable intake level set for the toxin. We highlight the data linking such low-level Cd intake with tubular injury, altered abundance of cytochromes P450 (CYPs) in the kidney and an expression of a hypertensive phenotype. We provide updated knowledge on renal and vascular effects of the eicosanoids 20-hydroxyeicosatetraenoic acid (20-HETE) and eicosatrienoic acids (EETs), which are biologically active metabolites from arachidonate metabolism mediated by certain CYPs in the kidney. We note the ability of Cd to elicit oxidative stress and to alter metal homeostasis notably of zinc which may lead to augmentation of the defense mechanisms involving induction of the antioxidant enzyme heme oxygenase-1 (HO-1) and the metal binding protein metallothionein (MT) in the kidney. We hypothesize that renal Cd accumulation triggers the host responses mediated by HO-I and MT in an attempt to protect the kidney against injurious oxidative stress and to resist a rise in blood pressure levels. This hypothesis predicts that individuals with less active HO-1 (caused by the HO-1 genetic polymorphisms) are more likely to have renal injury and express a hypertensive phenotype following chronic ingestion of low-level Cd, compared with those having more active HO-1. Future analytical and molecular epidemiologic research should pave the way to the utility of induction of heme oxygenases together with dietary antioxidants in reducing the risk of kidney injury and hypertension in susceptible people.

Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction?

Background: Widespread use of automated sensitive assays for thyroid hormones and thyroid-stimulating hormone (TSH) has increased identification of mild thyroid dysfunction, especially in elderly patients. The clinical significance of this dysfunction, however, remains uncertain, and associations with cognitive impairment, depression, and anxiety are unconfirmed. Objective: To determine the association between mild thyroid dysfunction and cognition, depression, and anxiety in elderly persons. Design: Cross-sectional study. Associations were explored through mixed-model analyses. Setting: Primary care practices in central England. Patients: 5865 patients 65 years of age or older with no known thyroid disease who were recruited from primary care registers. Measurements: Serum TSH and free thyroxine (T4) were measured. Depression and anxiety were assessed by using the Hospital Anxiety and Depression Scale (HADS), and cognitive functioning was established by using the Middlesex Elderly Assessment of Mental State and the Folstein Mini-Mental State Examination. Comorbid conditions, medication use, and sociodemographic profiles were recorded. Results: 295 patients met the criteria for subclinical thyroid dysfunction (127 were hyperthyroid, and 168 were hypothyroid). After confounding variables were controlled for, statistically significant associations were seen between anxiety (HADS score) and TSH level (P = 0.013) and between cognition and both TSH and free T4 levels. The magnitude of these associations lacked clinical relevance: A 50-mIU/L increase in the TSH level was associated with a 1-point reduction in the HADS anxiety score, and a 1-point increase in the Mini-Mental State Examination score was associated with an increase of 50 mIU/L in the TSH level or 25 pmol/L in the free T4 level. Limitations: Because of the low participation rate, low prevalence of subclinical thyroid dysfunction, and other unidentified recruitment biases, participants may not be representative of the elderly population. Conclusions: After the confounding effects of comorbid conditions and use of medication were controlled for, subclinical thyroid dysfunction was not associated with depression, anxiety, or cognition. © 2006 American College of Physicians.

The role of monocytes in atherosclerotic coronary artery disease

Inflammation plays a key role in the pathogenesis of atherosclerosis. The more we discover about the molecular pathways involved in atherosclerosis, the more we perceive the importance of monocytes in this process. Circulating monocytes are components of innate immunity, and many pro-inflammatory cytokines and adhesion molecules facilitate their adhesion and migration to the vascular endothelial wall. In addition to the accumulation of lipids and formation of atherogenic 'foam' cells, monocytes may promote atherosclerotic plaque growth by production of inflammatory cytokines, matrix metalloproteinases, and reactive oxidative species. However, the contribution of monocytes to atherogenesis is not only limited to tissue destruction. Monocyte subsets are also involved in intraplaque angiogenesis and tissue reparative processes. The aim of this overview is to discuss the mechanisms of monocyte activation, the pivotal role and importance of activated monocytes in atherosclerotic coronary artery disease, their implication in the development of acute coronary events, and their potential in cardiovascular reparative processes such angiogenesis.

Medical advice, diabetes self-management, and health outcomes of a multi-ethnic population from the National Health and Nutrition Examination Survey 2007--2008

Diabetes self-management, an essential component of diabetes care, includes weight control practices and requires guidance from providers. Minorities are likely to have less access to quality health care than White non-Hispanics (WNH) (American College of Physicians-American Society of Internal Medicine, 2000). Medical advice received and understood may differ by race/ethnicity as a consequence of the patient-provider communication process; and, may affect diabetes self-management. ^ This study examined the relationships among participants’ report of: (1) medical advice given; (2) diabetes self-management, and; (3) health outcomes for Mexican-Americans (MA) and Black non-Hispanics (BNH) as compared to WNH (reference group) using data available through the National Health and Nutrition Examination Survey (NHANES) for the years 2007–2008. This study was a secondary, single point analysis. Approximately 30 datasets were merged; and, the quality and integrity was assured by analysis of frequency, range and quartiles. The subjects were extracted based on the following inclusion criteria: belonging to either the MA, BNH or WNH categories; 21 years or older; responded yes to being diagnosed with diabetes. A final sample size of 654 adults [MA (131); BNH (223); WNH (300)] was used for the analyses. The findings revealed significant statistical differences in medical advice reported given. BNH [OR = 1.83 (1.16, 2.88), p = 0.013] were more likely than WNH to report being told to reduce fat or calories. Similarly, BNH [OR = 2.84 (1.45, 5.59), p = 0.005] were more likely than WNH to report that they were told to increase their physical activity. Mexican-Americans were less likely to self-monitor their blood glucose than WNH [OR = 2.70 (1.66, 4.38), p<0.001]. There were differences among ethnicities for reporting receiving recent diabetes education. Black, non-Hispanics were twice as likely to report receiving diabetes education than WNH [OR = 2.29 (1.36, 3.85), p = 0.004]. Medical advice reported given and ethnicity/race, together, predicted several health outcomes. Having recent diabetes education increased the likelihood of performing several diabetes self-management behaviors, independent of race. ^ These findings indicate a need for patient-provider communication and care to be assessed for effectiveness and, the importance of ongoing diabetes education for persons with diabetes.^

Changes in [18F]Fluoro-2-deoxy-D-glucose incorporation induced by doxorubicin and anti-HER antibodies by breast cancer cells modulated by co-treatment with metformin and its effects on intracellular signalling

Peer reviewed