New roles for renin and prorenin in heart failure and cardiorenal crosstalk

The renin-angiotensin-aldosterone-system (RAAS) plays a central role in the pathophysiology of heart failure and cardiorenal interaction. Drugs interfering in the RAAS form the pillars in treatment of heart failure and cardiorenal syndrome. Although RAAS inhibitors improve prognosis, heart failure–associated morbidity and mortality remain high, especially in the presence of kidney disease. The effect of RAAS blockade may be limited due to the loss of an inhibitory feedback of angiotensin II on renin production. The subsequent increase in prorenin and renin may activate several alternative pathways. These include the recently discovered (pro-) renin receptor, angiotensin II escape via chymase and cathepsin, and the formation of various angiotensin subforms upstream from the blockade, including angiotensin 1–7, angiotensin III, and angiotensin IV. Recently, the direct renin inhibitor aliskiren has been proven effective in reducing plasma renin activity (PRA) and appears to provide additional (tissue) RAAS blockade on top of angiotensin-converting enzyme and angiotensin receptor blockers, underscoring the important role of renin, even (or more so) under adequate RAAS blockade. Reducing PRA however occurs at the expense of an increase plasma renin concentration (PRC). PRC may exert direct effects independent of PRA through the recently discovered (pro-) renin receptor. Additional novel possibilities to interfere in the RAAS, for instance using vitamin D receptor activation, as well as the increased knowledge on alternative pathways, have revived the question on how ideal RAAS-guided therapy should be implemented. Renin and prorenin are pivotal since these are at the base of all of these pathways

THE DIFFERENTIAL DIAGNOSIS OF RENAL TUMOR BY THE URINARY ENZYME PATTERN

Up to the present time urinary enzymology has meant measuring the activity of single or a few enzymes out of collected urine. Its diagnostic value is small and is satisfactory only as a screening test. The diagnostic value of a urinary enzyme pattern was examined in renal tumors. After carefully selecting elements of the enzyme pattern we observed an important shift of relative proportions of single enzyme within the assayed pattern. This permitted, for the first time in urinary enzymology, a diagnosis. Such a shift of proportions has not been previously identified in man. Therefore we suggested the determination of a "direct enzyme" pattern. This has been defined and its advantages are as follows: 1.close correlation with the investigated pathological lesion. 2. No influence from other areas of the urogenital system. 3. Usual normal values and urinary collection are not necessary. The ideal form of urinary enzymology in man is diagnosis by an enzyme pattern from voided urine. Therefore it is necessary to demonstrate in future the correlation between tissue pattern and corresponding urinary enzyme pattern under identical conditions

Relationship between ventilatory function and age in master athletes and a sedentary reference population

Abstract Ageing is accompanied with a decline in respiratory function. It is hypothesised that this may be attenuated by high physical activity levels. We performed spirometry in master athletes (71 women; 84 men; 35–86 years) and sedentary people (39 women; 45 men; 24–82 years), and calculated the predicted lung age (PLA). The negative associations of age with forced expiratory volume in 1 s (FEV1; 34 mL·year−1) and other ventilatory parameters were similar in controls and master athletes. FEV1pred was 9 % higher (P<0.005) and PLA 15 % lower (P00.013) in athletes than controls. There were no significant differences between endurance and power athletes and sedentary people in maximal inspiratory and expiratory pressure. Neither age-graded performance nor weekly training hours were significantly related to lung age. Life-long exercise does not appear to attenuate the age-related decrease in ventilatory function. The better respiratory function in master athletes than age-matched sedentary people might be due to self-selection and attrition bias

Radiotherapy of painful heel spur with two fractionation regimens

Background In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5 Gy vs. a standard single dose of 1 Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6 Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective. Patients and methods A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 x 1 Gy twice a week, while the experimental group was treated with single fractions of 12 x 0.5 Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study's primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks. Results The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded. Conclusion Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 x 0.5 Gy was not superior to the current standard dose of 6 x 1 Gy. Further trials are necessary to explore the best fractionation schedule