Influence of Blood Pressure and Other Clinical Variables on Long-Term Mortality in a Cohort of Elderly Subjects with Type 2 Diabetes.

BACKGROUND: Diabetes mellitus and high blood pressure (HBP) are commonly associated conditions in the elderly population. An effect of treatments, biologic and anthropometric variables on long-term mortality is unknown in this population. OBJECTIVES: To determine the prevalence of HBP control in a sample of elderly patients with type 2 diabetes with office blood pressure (BP) readings and ambulatory blood pressure monitoring (ABPM) and evaluate the influence of BP, anthropometric and laboratory variables on long term mortality. METHODS: Cohort study in patients living at home in the area of Sherbrooke, ≥65 years old, receiving reimbursement for antidiabetic medication. The study included medical history, 2 sets of BP measurements, 2 24-hour urinary collections for microalbuminuria, 1 24-hour ABPM, blood level of creatinine and glycosylated hemoglobin. Charts were reanalyzed 8 years later for analysis of cardiovascular and total mortality cases. RESULTS: 198 patients were initially recruited. By history, 83% of the subjects had diagnoses and treatments for high blood pressure. In multivariate analysis, factors associated with an 8-year increased risk for cardiovascular mortality were creatinine ≥84 µmol/L, office seated systolic blood pressure ≤130 and diastolic BP ≤67.6 over 24 hours. Factors associated with total mortality were lower waist circumference, serum creatinine ≥84 and diastolic BP ≤67.6 over 24 hours. CONCLUSIONS: Lower systolic and diastolic BP (office and ABPM), lower waist circumference and higher creatinine values are associated with an increased mortality risk. This suggests that a lower BP, declining kidney function and frailty are factors associated with this observation.

Diabetes, Dementia and Hypoglycemia.

We are experiencing an epidemic of both diabetes and dementia among older adults in this country. The risk for dementia appears to be increased in patients with diabetes, and patients with dementia and diabetes appear to be at greater risk for severe hypoglycemia. In addition, there may be an increased risk for developing dementia by older patients with diabetes who have had episodes of severe hypoglycemia, although this issue is controversial. In this article, we review the factors that contribute to the increased risk for dementia in older adults with diabetes and outline the complex relationships between hypoglycemia and dementia.

Quantification of pyrethroids in environmental samples using NCI-GC-MS with stable isotope analogue standards.

Stable isotope internal standards are useful in correcting for matrix effects and instrumental variability when environmental samples such as wastewaters and biosolids are analyzed by mass spectral methods. This paper reports the use of deuterium-labeled analogues of eight pyrethroid insecticides to improve accuracy for the analysis of environmental samples by negative chemical ionization gas chromatography with mass spectrometric detection (NCI-GC-MS). Data for the analysis of effluent water from wastewater treatment facilities are presented which demonstrate that the method is rugged and capable of achieving limits of quantification (LOQs) as low as 0.5 ng/L (ppt), with individual recoveries within the range of 81-94% for those compounds with minimal control background concentrations. In addition, an alternate use of the deuterium-labeled standards is proposed for the determination of method recoveries at low levels that would normally have been precluded due to background pyrethroid levels present in environmental samples being used for control fortifications.

[Evaluation of circadian variation of blood pressure by ambulatory blood pressure monitoring in an elderly diabetic population with or without orthostatic hypotension]. / Évaluation des variations circadiennes de la tension artérielle par monitorage ambulatoire de la pression artérielle dans une population âgée diabétique atteinte ou non d'hypotension orthostatique.

Orthostatic hypotension is frequently observed in the elderly population and has been previously identified as a significant risk factor for increased mortality. The link between this condition and increased mortality could be due to an abnormal circadian pattern of blood pressure. The absence of a physiological nocturnal decrease in blood pressure is termed the non-dipping pattern. This abnormality is relatively frequent in elderly people suffering from orthostatic hypotension, but its prevalence in the diabetic geriatric population is unknown. The purpose of this study is to compare blood pressure profiles on ambulatory blood pressure monitoring (ABPM) in a sample of elderly diabetic subjects suffering from orthostatic hypotension with those without postural hypotension. One hundred and ninety-eight patients were recruited by mail. The presence or absence of orthostatic hypotension was determined. They all subsequently underwent ABPM. One hundred and thirty-one of our subjects (68%) suffered from orthostatic hypotension; of these, 76% had a non-dipping pattern on ABPM, compared with 74% of the subjects not suffering from orthostatic hypotension (P = NS). This study thus demonstrates the high prevalence of orthostatic hypotension in an elderly diabetic population. On the other hand, we could not demonstrate a correlation between the non-dipping pattern and the presence of orthostatic hypotension. This is in contrast with previous work done in a non-diabetic elderly population. Further studies are needed to determine the effect of diabetes on blood pressure.

Antioxidant-rich food intakes and their association with blood total antioxidant status and vitamin C and E levels in community-dwelling seniors from the Quebec longitudinal study NuAge.

A cross-sectional study was designed to investigate the association between current consumption of a series of 26 common antioxidant-rich foods (ARF) with serum total antioxidant status (TAS) and plasma vitamin C and E levels in community-dwelling older adults. A convenience sample of the first 94 non-smoking Caucasian men (54%) and women (46%) enrolled in the Quebec Longitudinal Study NuAge were selected. The "Functional Foods Consumption Frequency Questionnaire" (FFCFQ) was administered at recruitment (T1) to ascertain patterns of consumption of ARF over the lifetime. The total Oxygen Radical Antioxidant Capacity (ORAC) of 25 ARF reported by subjects was estimated using published values. Serum TAS was determined based on the Trolox equivalent antioxidant capacity (TEAC) assay while plasma vitamins C and E (α- and γ-tocopherol) levels were analyzed by HPLC. The numbers of ARF eaten daily at T1, estimated from the FFCFQ and calculated from the diet recalls, were significantly correlated (r=0.51, P<0.0001) and each measure was associated with total ORAC content (r=0.34, P<0.001 and r=0.59, P<0.0001 for FFCFQ and recalls, respectively). No significant association was found between TAS and the total ORAC value of ARF determined from the quantitative 24-h diet recalls. However, daily ARF consumption at T1 obtained from the FFCFQ was significantly and positively correlated with TAS (r=0.26, P<0.05) and circulating levels of vitamin C (r=0.25, P<0.02) and α-tocopherol (r=0.22, p<0.05) and negatively correlated with plasma γ-tocopherol (r=-0.25, P<0.025). These results highlight associations between ARF consumption and circulating levels of antioxidants in the elderly and suggest benefits from antioxidant-rich foods during aging.

Effects of vitamin C supplementation on antioxidants and lipid peroxidation markers in elderly subjects with type 2 diabetes.

The objective of our study was to evaluate the effects of the administration of two dosages of vitamin C (Vit-C) (0.5 and 1g/day, vs. placebo) in elderly patients with type 2 diabetes mellitus on the intracellular levels of Vit-C and glutathione, and on the lipid peroxidation markers and vitamin E (Vit-E) content of low-density lipoprotein (LDL) and on LDL susceptibility to gamma radiolysis-induced peroxidation. Thirty-six patients were randomized into three groups. In patients on 0.5 g Vit-C/day versus the placebo group, a significant increase in cellular reduced glutathione level was observed (0.60+/-0.26 vs. 0.33+/-0.27). In patients on 1 g Vit-C/day versus placebo, a significant increase was also observed in cellular reduced glutathione (0.93+/-0.70 vs. 0.33+/-0.27), in Vit-C (5.66+/-2.00 vs. 2.72+/-1.88) and in vitamin E content of LDL (1.98+/-0.38 vs. 1.48+/-0.40). No change was observed in either group in basal levels of lipid peroxidation markers and in the susceptibility of LDL to peroxidation provoked by gamma-radiolysis. In conclusion, Vit-C has a dose-dependent effect on the cellular contents of antioxidants and on vitamin E content of LDL in elderly patients with type 2 DM. These changes are not sufficient to decrease the LDL susceptibility to peroxidation.

Comparison of pharmacokinetic and pharmacodynamic profiles of aspirin following oral gavage and diet dosing in rats.

Aspirin is one of the oldest drugs and has been purported to have multiple beneficial effects, including prevention of cardiovascular disease and cancer, in addition to its original indication for treatment of inflammation, fever and pain. In cancer chemoprevention studies using animal models, two methods of aspirin administration have been employed: oral gavage and diet. The untested assumption was that exposure and the resultant pharmacological effects are similar for these two administration methods when dosing is normalized on the basis of mg/kg body weight/day. This study examined and compared time-dependent plasma and colon mucosal concentrations of aspirin metabolite salicylate (aspirin concentrations were below level of quantification), plasma thromboxane B(2) concentrations, and colon mucosal prostaglandin E(2) concentration following these two different dosing paradigms in rats. Diet dosing yielded relatively constant plasma and colon salicylate concentration vs. time profiles. On the other hand, oral gavage dosing led to a rapid peak followed by a fast decline in salicylate concentration in both plasma and colon. Nevertheless, the exposure as measured by the area under plasma or colon concentration-time curve of salicylate was linearly related to dose irrespective of the dosing method. Linear relationships were also observed between colon and plasma salicylate areas under the curve and between colon prostaglandin E(2) and plasma thromboxane B(2) areas under the curve. Therefore, more easily accessible plasma salicylate and thromboxane B(2) concentrations were representative of the salicylate exposure and prostaglandin E(2) pharmacodynamic biomarker in the target colon, respectively.

Activation of MAP kinases by hexavalent chromium, manganese and nickel in human lung epithelial cells.

Epidemiological studies indicate that workers who perform welding operations are at increased risk for bronchitis, siderosis, occupational asthma and lung cancer due to fume exposure. Welding fumes are a complex chemical mixture, and the metal composition is hypothesized to be an etiological factor in respiratory disease due to this exposure. In the present study, human lung epithelial cells in vitro responded to hexavalent chromium, manganese and nickel over a concentration range of 0.2-200 microM with a significant increase in intracellular phosphoprotein (a measure of stress response pathway activation). The mitogen-activated protein kinases ERK1/2, SAPK/JNK and p38 were activated via phosphorylation following 1-h exposures. Hexavalent chromium up-regulated p-38 phosphorylation 23-fold and SAPK/JNK phosphorylation 17-fold, with a comparatively modest 4-fold increase in ERK1/2 phosphorylation. Manganese caused a two- to four-fold increase in SAPK/JNK and ERK 1/2 phosphorylation, with no observed effects on p38 kinase. Nickel caused increased (two-fold) phosphorylation of ERK 1/2 only, and was not cytotoxic over the tested concentration range. The observed effects of welding fume metals on cellular signaling in lung epithelium demonstrate a potentially significant interplay between stress-response signaling (p38 and SAPK/JNK) and anti-apototic signaling (ERK 1/2) that is dependant on the specific metal or combination of metals involved.

Cytotoxicity of chromium and manganese to lung epithelial cells in vitro.

Chromium, nickel and manganese are the predominant metals in welding fumes and are associated through epidemiological studies with an increased risk for developing occupational asthma due to welding activities. Here, we show that chromium(VI) and manganese, but not nickel, are cytotoxic to normal human lung epithelial cells in vitro (SAEC and BEAS-2B), at concentration ranges of 0.2-200 microM. The toxic effect was associated with increased levels of intracellular phosphoprotein and subsequent release of inflammatory cytokines IL-6 and IL-8, while no release of TNF-alpha was observed. Changes in intracellular phosphoprotein levels occurred at concentrations below the cytotoxic effect. IL-6 and IL-8 production increased up to 4.4-fold relative to controls. IL-6 and IL-8 are released from lung epithelium to recruit cells of the immune system to sites of tissue damage. Therefore, the observed effects of chromium(VI) and manganese in lung epithelial cells demonstrate a mechanism through which the toxicity of these metals to epithelial cells can result in recruitment of cells of the immune system.

Estrogenic action of ß-HCH through activation of c-Neu in MCF-7 breast carcinoma cells.

ß-HCH is known to be a poor agonist for the estrogen receptor (ER), and yet it has been shown to act like an estrogen in stimulating foci formation in MCF-7 cells. We investigated the reason for such an action of ß-HCH, using a rat prolactin-luciferase reporter system transfected to MCF-7 cells. We found that the presence of c-Neu (erbB2), ER and ERE is needed for ß-HCH to act estrogenic at the transcription activation level in this cell line. We compared the action of ß-HCH to that of EGF which is known to act estrogenic without being an agonist for ER in this cell and found that their action patterns are quite similar, the only difference being that the former action is blocked by an antibody against c-Neu and the latter by both c-Neu and EGF receptor antibody. We concluded that ß-HCH's estrogenic action in this cell model is mediated through "ligand-independent activation of ER pathway".