Mini nutritional assessment as a useful method of predicting the development of pressure ulcers in elderly inpatients.

OBJECTIVES: To determine the usefulness of the Mini Nutritional Assessment (MNA) and plasma amino acid analysis in predicting the formation of pressure ulcers (PUs) in inpatients. DESIGN: Prospective, observational cohort study with a mean observation period of 62.2 ± 86.4 days. SETTING: Intermediate and acute care wards of a hospital in rural Japan. PARTICIPANTS: Inpatients with an average age of 85.0 ± 7.6 (N = 422). MEASUREMENTS: Mini Nutritional Assessment, Subjective Global Assessment (SGA), Braden Scale (PU prognostic score), PU formation, and biochemical analysis including plasma amino acid concentrations. RESULTS: PUs developed in 7.1% of participants. A MNA score of less than 8 was more sensitive than a rating of moderate or severe malnourishment on the SGA combined with a Braden Scale score of less than 15 in predicting future PUs. The area under the receiver operating characteristic curve (AUC) of the MNA was superior to that of the Braden Scale. The Braden Scale nutrition subscore had the lowest AUC of the six Braden Scale subscores. Individuals who developed PUs had significantly lower plasma arginine concentrations than those who did not. CONCLUSION: Mini Nutritional Assessment was able to predict the development of PUs. A MNA score of less than 8 performed better than the SGA, Braden Scale, and plasma arginine levels in predicting PU development. Although lower plasma arginine concentration at time of admission was associated with PU development, the AUC for arginine was not significantly different from 0.50. The findings from this prospective study support the use of nutritional assessment in inpatients to predict PU risk and target appropriate interventions.

Pharmacokinetic and pharmacodynamic interaction of nadolol with itraconazole, rifampicin and grapefruit juice in healthy volunteers.

To evaluate effects of itraconazole, rifampicin and grapefruit juice on pharmacokinetics and pharmacodynamics of a hydrophilic non-selective ß-adrenoceptor blocker nadolol, we conducted an open-label, four-way crossover study in 10 healthy male volunteers. A single oral dose of 30 mg nadolol was administered with water (control), itraconazole (100 mg), or grapefruit juice (300 mL), or after a 6-day pretreatment with rifampicin (450 mg/day). Plasma concentrations and urinary excretions of nadolol were measured over 48 hours after its dosing. Systolic and diastolic blood pressures and pulse rate were periodically recorded after nadolol administration as pharmacodynamic parameters. Itraconazole increased the peak plasma concentration and the area under the plasma concentration-time curve (AUC0-∞ ) of nadolol by 468% and 224% of control, respectively (P < .001). A slight, but not statistically significant, decrease in AUC0-∞ of nadolol was observed in rifampicin and grapefruit juice phases as compared to control. Elimination half-life for nadolol did not differ among the four phases. During itraconazole phase, nadolol reduced pharmacodynamic parameters to a greater extent than the other phases. These results suggest that itraconazole substantially increases the oral availability of nadolol possibly by the inhibition of intestinal P-glycoprotein, whereas grapefruit juice has little effect on nadolol pharmacokinetics.

Hypertension-Related Gene Polymorphisms of G-Protein-Coupled Receptor Kinase 4 Are Associated with NT-proBNP Concentration in Normotensive Healthy Adults.

G protein-coupled receptor kinase 4 (GRK4) with activating polymorphisms desensitize the natriuric renal tubular D1 dopamine receptor, and these GRK4 polymorphisms are strongly associated with salt sensitivity and hypertension. Meanwhile, N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in detecting slight volume expansion. However, relations between hypertension-related gene polymorphisms including GRK4 and cardiovascular indices such as NT-proBNP are not clear, especially in healthy subjects. Therefore, various hypertension-related polymorphisms and cardiovascular indices were analyzed in 97 normotensive, healthy Japanese adults. NT-proBNP levels were significantly higher in subjects with two or more GRK4 polymorphic alleles. Other hypertension-related gene polymorphisms, such as those of renin-angiotensin-aldosterone system genes, did not correlate with NT-proBNP. There was no significant association between any of the hypertension-related gene polymorphisms and central systolic blood pressure, cardioankle vascular index, augmentation index, plasma aldosterone concentration, or an oxidative stress marker, urinary 8-OHdG. Normotensive individuals with GRK4 polymorphisms show increased serum NT-proBNP concentration and may be at a greater risk of developing hypertension and cardiovascular disease.

Angiotensin III stimulates aldosterone secretion from adrenal gland partially via angiotensin II type 2 receptor but not angiotensin II type 1 receptor.

Angiotensin II (Ang II) and Ang III stimulate aldosterone secretion by adrenal glomerulosa, but the angiotensin receptor subtypes involved and the effects of Ang IV and Ang (1-7) are not clear. In vitro, different angiotensins were added to rat adrenal glomerulosa, and aldosterone concentration in the medium was measured. Ang II-induced aldosterone release was blocked (30.3 ± 7.1%) by an Ang II type 2 receptor (AT2R) antagonist, PD123319. Candesartan, an Ang II type 1 receptor (AT1R) antagonist, also blocked Ang II-induced aldosterone release (42.9 ± 4.8%). Coadministration of candesartan and PD123319 almost abolished the Ang II-induced aldosterone release. A selective AT2R agonist, CGP42112, was used to confirm the effects of AT2R. CGP42112 increased aldosterone secretion, which was almost completely inhibited by PD123319. In addition to Ang II, Ang III also induced aldosterone release, which was not blocked by candesartan. However, PD123319 blocked 22.4 ± 10.5% of the Ang III-induced aldosterone secretion. Ang IV and Ang (1-7) did not induce adrenal aldosterone secretion. In vivo, both Ang II and Ang III infusion increased plasma aldosterone concentration, but only Ang II elevated blood pressure. Ang IV and Ang (1-7) infusion did not affect blood pressure or aldosterone concentration. In conclusion, this report showed for the first time that AT2R partially mediates Ang III-induced aldosterone release, but not AT1R. Also, over 60% of Ang III-induced aldosterone release may be independent of both AT1R and AT2R. Ang III and AT2R signaling may have a role in the pathophysiology of aldosterone breakthrough.

Salt sensitivity is associated with insulin resistance, sympathetic overactivity, and decreased suppression of circulating renin activity in lean patients with essential hypertension.

BACKGROUND: The mechanisms by which a derangement of glucose metabolism causes high blood pressure are not fully understood. OBJECTIVES: This study aimed to clarify the relation between salt sensitivity of blood pressure and insulin resistance, which are important subcharacteristics of hypertension and impaired glucose metabolism, respectively. Effects on the renin-angiotensin and sympathetic nervous systems were also studied. DESIGN: The state of glucose metabolism was assessed by a hyperinsulinemic euglycemic glucose clamp technique and a 75-g oral-glucose-tolerance test in 24 essential hypertensive patients who were lean and without diabetes or chronic kidney disease. The subjects were classified as salt-sensitive or salt-resistant on the basis of the difference (Delta mean blood pressure > or =5%) between 24-h ambulatory blood pressure monitoring results on the seventh day of low-salt (34 mmol/d) and high-salt (252 mmol/d) diets. Urine and blood samples were collected for analyses. RESULTS: There was a robust inverse relation between the glucose infusion rate (GIR) and the salt sensitivity index. The GIR correlated directly with the change in urinary sodium excretion and was inversely related to the change in hematocrit when the salt diet was changed from low to high, which is indicative of salt and fluid retention in salt-sensitive subjects. The GIR also showed an inverse correlation compared with the changes in urinary norepinephrine excretion, plasma renin activity, and plasma aldosterone concentration. CONCLUSIONS: Salt sensitivity of blood pressure is strongly associated with insulin resistance in lean, essential hypertensive patients. Hyperinsulinemia, sympathetic overactivation, and reduced suppression of the renin-angiotensin system may play a role in this relation.