The angiotensin II (AII) antagonist [Sar1-Ala8]AII (Saralasin) was injected into the brain ventricles (IVT) and intravenously (IV) in five different types of hypertensive unanesthetized rats. Renal hypertension was studied 16-22 days after kidney clipping. Intravenous infusions of cumulative doses (0.1-100 microgram/kg per min) and IVT injections (5-40 microgram) of Saralasin did not change mean arterial pressure (MAP) in controls and in one-clip, one-kidney Goldblatt hypertension, whereas MAP decreased in one-clip, two-kidney Goldblatt hypertension following IV and IVT Saralasin. In two-clip, two kidney hypertensive rats, IVT Saralasin decreased MAP but was ineffective when infused IV. Both IV and IVT Saralasin increased MAP in DOC hypertension. In spontaneously hypertensive (SH) rats, IV Saralasin increased MAP; IVT injection decreased MAP. The effect of IVT Saralasin in SH rats persisted 15-20 h after nephrectomy. We conclude that plasma AII may contribute to peripheral and central mechanisms of blood pressure regulation. The dissociation of the effects of IV and IVT Saralasin and the persistance of blood pressure decrease in nephrectomized SH rats following IVT Saralasin further support a role for locally formed brain angiotensin.

The effects of angiotensin (AT)(1) receptor antagonists on functional and morphological alterations associated with atherosclerosis are not well known. The current study was performed to examine the long-term effects of valsartan (3 or 10 mg/kg per day for 10 weeks) on endothelial function and structural changes in aorta from rabbits fed with either a control diet or a cholesterol-enriched diet. Rabbits fed with the cholesterol-rich diet showed higher (P<0.05) plasma levels of cholesterol than did controls. Treatment with valsartan (3 or 10 mg/kg per day) did not alter plasma cholesterol levels or systolic arterial pressure in any group. Contractions induced by angiotensin II were comparable in both control and hypercholesterolemic rabbits and were markedly reduced by treatment with valsartan. Relaxations induced by acetylcholine were lower in hypercholesterolemic rabbits than in controls. Treatment with valsartan (3 or 10 mg/kg per day) enhanced (P<0.05) this response in hypercholesterolemic rabbits but not in controls. Lumen and media cross-sectional areas were comparable in control and hypercholesterolemic rabbits. Vessel area was higher (P<0.05) in hypercholesterolemic rabbits than in controls. Intimal lesion was 29.5+/-6% in cholesterol-fed rabbits and nonexistent in control rabbits. Treatments with 3 and 10 mg/kg per day valsartan reduced (P<0.05) intimal lesion to 2.4+/-0.7% and 2.7+/-0.9%, respectively, and increased lumen area in hypercholesterolemic rabbits. No changes in either vessel or media cross-sectional areas were observed in these animals. In summary, angiotensin II, through AT(1) receptors, appears to play a key role in the development of the vascular functional and structural changes associated with hypercholesterolemia. AT(1) receptor antagonists, besides their antihypertensive effects, could be an important therapeutic tool to reduce the development of atherosclerosis.

Purpose Two-thirds of cancer patients report taste disorders during and after chemotherapy. Taste disorders impact on nutritional status which is highly relevant for treatment efficacy and overall prognosis. Improvement of taste disorder is of particular importance for cancer patients’ outcomes, thus the TASTE trial was conducted to improve taste disorders with a taste and smell training. Methods In this trial, patients undergoing chemotherapy were screened for taste disorders. Subsequently, patients were allocated based on the detection of taste disorders (≤8 taste strips points) to an intervention group with a taste and smell training at baseline and week 3–5 or were only followed up, if no taste disorder was detected (≥9 taste strips points) (non-intervention group). At baseline, all patients received a nutritional counseling. The primary endpoint was the minimal clinically relevant improvement of taste strips score by 2 taste strips points in at least 50% of the patients with taste disorders. Results The trial included 62 patients (48 women [77%], 14 male [23%], age 54.5±11.6 years) who had gastrointestinal (n=29), breast (n=31), or lung cancer (n=2). Taste disorders were more frequent in gastrointestinal than in breast cancer patients. Out of 62 patients screened, 30 patients showed taste disorders. The primary endpoint was met with 92% (n=23 of 25) of the patients completing the intervention. In the intervention group, the patients’ taste significantly improved from baseline (median taste strips: 7.0 points) to week 12 (median taste strips: 10.0 points) ( P ≤0.001). Patients of the non-intervention group who completed the reassessment (n=27 of 32) experienced no change in taste perception in the 3-month follow-up ( P =0.897). Conclusion Intensified nutritional counseling with taste and smell training may improve taste perception of patients undergoing chemotherapy. A confirmatory randomized trial is planned.

Background: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or diseaserelated, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population.

Objective: To explore whether a structured counselling-based intervention increases vigorous physical activity behaviour of adolescent and young adult cancer survivors. Design: Randomized controlled phase II trial. Setting: University Cancer Center Hamburg, Germany. Subjects: Eighty-nine participants (mean age 24.1 ± 6.3) were randomized to control ( n = 44) or intervention group ( n = 45). Interventions: The intervention group was consulted about physical activity behaviour via interview (week 0), and telephone counselling (weeks 1, 3 and 12). The control group only received general physical activity guidelines for cancer survivors (week 0). Main measures: The primary outcome was the rate of participants with ⩾9 metabolic equivalent (MET)-hours per week of vigorous activity post-intervention, measured with the International Physical Activity Questionnaire. Secondary outcomes included assessing physical activity behaviour (e.g. amount and type of physical activity) and quality of life. Assessments were completed in weeks 0 (baseline), 12 (post-intervention) and 52 (follow-up). Results: Sixty-nine participants completed the post-intervention- and 47 the follow-up-assessment. The rate of participants performing vigorous physical activity increased from baseline to post-intervention for both without differing significantly ( P = 0.541). Both increased their total metabolic equivalent from baseline to post-intervention (intervention group from 55.2 ± 43.7 to 61.7 ± 29.4, control group from 75.3 ± 81.4 to 88.3 ± 80.2). At follow-up the intervention group (73.7 ± 80.2) was more active than baseline when compared to the control group (78.5 ± 50.0). Conclusions: A structured counselling-based physical activity intervention did not significantly impact the level of vigorous physical activity behaviour in adolescent and young adult cancer survivors.

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.

Three antisera are reported that reacted with all cells tested except the donor’s own and those from K(0) people. Each serum reacted with the cells of the other two donors. The nature of the association of the three antibodies with the Kell system remains unknown.

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