Lavender

A collection of creative writing

Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 μg/kg body weight/day or 70 μg/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge

Stress-induced changes in the expression of monocytic β2-integrins: The impact of arousal of negative affect and adrenergic responses to the Anger Recall Interview

Adhesion of circulating monocytes to the vascular endothelium is one of the earliest steps in the development of atherosclerosis. This leukocyte-to-endothelium interaction is mediated in part by β2-integrins, a group of cell adhesion molecules that bind to endothelial ligands. Given the significance of this interaction to atherogenesis, we examined the effects of stress, operationalized as the arousal of negative affect (NA) and cardiovascular and catecholamine responses to the Anger Recall Interview (ARI), on the expression of LFA-1 (CD11a), Mac-1 (CD11b) and p150/95 (CD11c) on circulating monocytes (CD14+). Subjects were 173 healthy, nonsmoking men and women (60% men, 40% minorities, aged 18–49 year). Arousal of NA, cardiovascular responses (heart rate [HR], systolic blood pressure [SBP], diastolic blood pressure [DBP]), circulating catecholamines (epinephrine [Epi], norepinephrine [Ne]) and β2-integrin (CD11/CD18) expression were determined prior to and following the ARI. The principal findings were that the ARI, on average, induced a decrease in monocyte expression of β2-integrins. However, after adjusting for age, sex, body mass index, exercise status, and baseline level of β2-integrin expression, those individuals who showed the largest increases in NA, Ne and DBP during the ARI showed an increase in monocyte β2-integrin expression. Thus, heightened psychological and physiological stress responses induced phenotypic changes in monocytic expression of β2-integrins that are consistent with the role of monocytes/macrophages in vascular inflammation and increased risk of atherosclerotic cardiovascular disease

Solution structure of the inner DysF domain of myoferlin and implications for limb girdle muscular dystrophy type 2b

Mutations in the protein dysferlin, a member of the ferlin family, lead to limb girdle muscular dystrophy type 2B and Myoshi myopathy. The ferlins are large proteins characterised by multiple C2 domains and a single C-terminal membrane-spanning helix. However, there is sequence conservation in some of the ferlin family in regions outside the C2 domains. In one annotation of the domain structure of these proteins, an unusual internal duplication event has been noted where a putative domain is inserted in between the N- and C-terminal parts of a homologous domain. This domain is known as the DysF domain. Here, we present the solution structure of the inner DysF domain of the dysferlin paralogue myoferlin, which has a unique fold held together by stacking of arginine and tryptophans, mutations that lead to clinical disease in dysferlin

Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells

Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl2 and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl2 concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis