Abstract-The basic requirement for declaring an association study positive is that the "hypertension-favoring" allele is more frequent in hypertensive cases than in normotensive controls. However, both positive and negative associations with hypertension have been found for the same polymorphism when studied in different populations. In the present study, we addressed the question of the possible cause(s) of this discrepancy among populations by using the ␣-adducin polymorphism as a paradigm. Four hundred ninety hypertensives and 176 normotensives enrolled in Sassari, Italy, and 468 hypertensives and 181 normotensives enrolled in Milano, Italy, were genotyped for the ␣-adducin Gly460Trp polymorphism. The blood pressure response to 2 months of hydrochlorothiazide therapy could be evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with and without the 460Trp ␣-adducin allele. The ␣-adducin 460Trp allele was not significantly more frequent in hypertensives in the Sassari population but was more frequent in hypertensives than in normotensives in Milano (Pϭ0.019). Basal plasma renin activity was lower and blood pressure fall after diuretic therapy more pronounced (PϽ0.01) in hypertensives carrying at least one 460Trp allele than in Gly460Gly homozygotes, irrespective of their membership in the Sassari or Milano cohort. The effect of ␣-adducin genotype in predicting basal plasma renin activity and blood pressure decrease with diuretic treatment is similar in Sassari and Milano, despite the lack of association of the ␣-adducin genotype with hypertension in Sassari. (Hypertension. 1999;34:649-654.)

The study analyzes the prevalence of cardiovascular risk factors in 1343 patients with severe headache (399 men and 944 women), aged 15 to 64 years; analyses were controlled for sex, age, and type and frequency of headache. Prevalence of various forms of headache was different between men and women. Age and days per year with headache were significantly different among various forms of headache. For men and women with headache, age directly related to prevalence of hypertension, hypercholesterolemia, and obesity. Due to low prevalence, analyses by age were not done for diabetes mellitus. For cigarette smoking, prevalence was not related to age in men, but was inversely related to age in women. With control for age, prevalence of cardiovascular risk factors was not significantly different among patients with different forms of headache, except for cluster headache. Among men with cluster headache, prevalence was high for cigarette smoking, but low for hypercholesterolemia. With control for age, days per year with headache did not relate to prevalence of cardiovascular risk factors except for cigarette smoking in men. Compared to data for a population sample used as control, patients with headache had higher prevalence of hypertension in both sexes, independent of age (odds ratio 1.51, 95% confidence interval 1.28 to 1.80); the difference between patients with headache and the control population was lower with increasing age. The high prevalence of hypertension among patients with headache was not due to overweight. The data indicate that headache is significantly associated with hypertension, but not with other cardiovascular risk factors.

Transcriptional deregulation of genes encoding for H(2)S-producing enzymes is present in uraemia. Although the specificity of the method employed for H(2)S detection is low, the finding that H(2)S is decreased is complemented by the lower sulphhaemoglobin levels. Potential implications of this study relate to the pathogenesis of the uraemic syndrome manifestations, such as hypertension and atherosclerosis.

In middle-aged adults, high protein intake is associated cross-sectionally with higher GFR but longitudinally with greater GFR decline over time.

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Background Lab tests on saliva could be useful because of low invasivity. Previous reports indicated that creatinine, uric acid, and potassium are measurable in saliva. For these analytes the study investigated methodology of saliva tests and correlations between plasma and saliva levels. Methods The study enrolled 15 healthy volunteers for methodological analyses and 42 nephropathic patients for plasma-saliva correlations (35 non-dialysis and 7 dialysis). Saliva was collected by synthetic swap right after venipuncture for blood withdrawal. Blood and saliva, unless otherwise indicated, were collected early in the morning after overnight fast and lab tests were performed in fresh samples by automated biochemistry (standard). Methodological analyses included blind duplicates, different collection mouth sites, day-to-day variability, different collection times, and freezing-thawing effects. Analyses on plasma-saliva correlations included post-dialysis changes. Results For saliva lab tests of all analytes, blind duplicates, samples from different mouth sites or of different days were not significantly different but were significantly correlated (differences ≤14.4%; R ≥ 0.620, P ≤ 0.01). For all analytes, mid-morning saliva had lower levels than but correlated with standard saliva (differences ≥15.8%; R ≥ 0.728, P ≤ 0.01). Frozen-thawed saliva had lower levels than fresh saliva for uric acid only (− 17.2%, P < 0.001). Frozen-thawed saliva correlated with fresh saliva for all analytes (R ≥ 0.818, P ≤ 0.001). Saliva and plasma levels differed but correlated with plasma for creatinine (R = 0.874, P < 0.001), uric acid (R = 0.821, P < 0.001) and potassium (R = 0.767, P < 0.001). Post-dialysis changes in saliva paralleled post-dialysis changes in plasma. Conclusion Saliva levels of creatinine, uric acid, and potassium are measurable and correlated with their plasma levels. Early morning fasting fresh saliva samples are advisable because later collection times or freezing lower the saliva levels of these analytes.

RationaleThe cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties.ObjectiveAim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels.Methods and ResultsTreated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2.ConclusionsTreatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling.

Abstract. Plasma proteins in hemodialysis patients display a significant increase in deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of protein fatigue damage. This has been linked to the toxic effects of hyperhomocysteinemia in uremic erythrocytes; however, treatment aimed at abating homocysteine levels did not lead to significant reductions in plasma protein damage. The hypothesis that lack of reduction in protein damage could be due to protein increased intrinsic instability, as result of interference with the uremic milieu rather than to hyperhomocysteinemia, was put forward. The deamidated/isomerized Asx content of normal plasma incubated with several uremic toxins for 24 h, 72 h, and 7 d was measured, identifying a group of toxins that were able to elicit this kind of damage. Uremic toxins were also incubated with purified human albumin, and dose-response experiments with the two most toxic agents in terms of protein damage (guanidine and guanidinopropionic acid) were carried out. The effect of the hemodialysis procedure on protein damage was evaluated. For investigating also the consequences of these alterations, human albumin was treated in vitro to produce an increase in deamidated/isomerized Asx residues, and the effects of albumin deamidation on protein binding were evaluated.