of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cy rat kidneys. Am J Physiol Renal Physiol 290: F897-F904, 2006. First published October 18, 2005 doi:10.1152/ajprenal.00332.2005.-Renal prostanoids are important regulators of normal renal function and maintenance of renal homeostasis. In diseased kidneys, renal cylooxygenase (COX) expression and prostanoid formation are altered. With the use of the Han:Sprague-Dawley-cy rat, the aim of this study was to determine the relative contribution of renal COX isoforms (protein, gene expression, and activity) on renal prostanoid production [thromboxane B 2 (TXB2, stable metabolite of TXA2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1␣ (6-keto-PGF1␣, stable metabolite of PGI 2)] in normal and diseased kidneys. In diseased kidneys, COX-1-immunoreactive protein and mRNA levels were higher and COX-2 levels were lower compared with normal kidneys. In contrast, COX activities were higher in diseased compared with normal kidneys for both COX-1 [0.05 Ϯ 0.02 vs. 0.45 Ϯ 0.11 ng prostanoids ⅐ min Ϫ1 ⅐ mg protein Ϫ1 (P Ͻ 0.001)] and COX-2 [0.64 Ϯ 0.10 vs. 2.32 Ϯ 0.22 ng prostanoids ⅐ min Ϫ1 ⅐ mg protein Ϫ1 (P Ͻ 0.001)]. As the relative difference in activity was greater for COX-1, the ratio of COX-1/COX-2 was higher in diseased compared with normal kidneys, although the predominant activity was still due to the COX-2 isoform in both genotypes. Endogenous and steady-state in vitro levels of prostanoids were ϳ2-10 times higher in diseased compared with normal kidneys. The differences between normal and diseased kidney prostanoids were in the order of TXB 2 Ͼ 6-keto-PGF 1␣ Ͼ PGE2, as determined by higher renal prostanoid levels and COX activity ratios of TXB 2/6-keto-PGF1␣, TXB2/PGE2, and 6-keto-PGF 1␣/PGE2. This specificity in both the COX isoform type and for the prostanoids produced has implications for normal and diseased kidneys in treatments involving selective inhibition of COX isoforms. thromboxane; prostaglandin CYCLOOXYGENASE (COX

Dietary soya protein substitution for casein initiated at weaning slows disease progression in animal models of chronic renal disease. As there is increasing evidence that fetal programming can have a significant impact on kidney physiology and function in offspring, the objective of the current study was to determine whether exposure to soya protein in the diet earlier than weaning would have further benefits. Han:SPRD-cy (cy/þ ) breeder rats were fed a casein-based or soya protein-based diet 2 weeks prior to mating, throughout pregnancy and during lactation. Following this maternal period, 3-week-old pups were given either the same or the alternate diet for a 7-week weaning period. Dietary soya protein compared with casein in the maternal or weaning period both independently resulted in less renal inflammation (macrophage infiltration lower by 24 % (P¼ 0·0003) and 32 % (P, 0·0001), respectively). When soya protein was given in both feeding periods, the effect was additive. Soya protein substitution for casein resulted in less oxidative damage as indicated by 28 % lower oxidized-LDL staining (P¼ 0·013) when present in the maternal period, or in the weaning period (by 56 %, P,0·0001). Renal cell proliferation was reduced by 29-33 % (P,0·05) in rats given soya protein whether the exposure was during the maternal or weaning period. Soya protein compared with casein in the maternal period also resulted in 33 % (P¼ 0·0013) less proteinuria, indicating superior renal function. Dietary soya protein during pregnancy and lactation represents a potential preventative approach in treating for those with congenital kidney diseases.

Dietary flax oil (FO) retards disease progression in growing or adult animal models of kidney disease. To determine whether dietary flax oil during the perinatal period would alter renal disease progression in offspring, Han-SPRD-cy rats with inherited cystic kidney disease were given diets with either 7% FO or corn oil (CO), throughout pregnancy and lactation. At 3 wk of age, offspring were then given either the same or the alternate diet for 7 wk. Rats given FO during the maternal period had 15% less renal cyst growth compared with rats given FO only in the postweaning period. Dietary FO, compared with CO, in the maternal period also resulted in 12% lower cell proliferation and 15% less oxidant injury in diseased kidneys of offspring. Including FO in both the maternal and postweaning period resulted in 29 -34% less renal interstitial fibrosis and 22-23% lower glomerular hypertrophy. Along with improved histology, these rats exhibited 13% less proteinuria and 30% lower creatinine clearance when dietary FO was given in the maternal period. The potential for dietary FO during pregnancy and lactation to positively modulate adult renal disease has significant implications for the 1 in 1000 individuals with congenital cystic kidney disease.

Background/Aims: Dietary soy protein and flax oil retard kidney disease progression when initiated in the early stages of disease in several experimental models, including the Han:SPRD-cy rat. However, individuals with kidney disease often do not become aware of their condition until injury to the kidney is extensive. The objective of this study was to determine whether initiating these interventions in established disease would alter further progression of renal injury. Methods: Two-month-old adult male Han:SPRD-cy rats were given either a flax oil diet (7% flax oil), a soy protein diet (20% soy protein) or a control diet (7% corn oil, 20% casein) for 4 months. Renal disease progression was assessed by examining morphological, immunohistochemical and biochemical parameters. Results: Compared to controls, there was 21–24% less staining of proliferating cells, 21–24% less oxidative damage and 13–15% less renal inflammation in kidneys from rats given dietary soy protein and flax oil. Renal cystic growth and fibrosis and serum creatinine levels were not altered by these dietary treatments. Conclusions: Late intervention with dietary soy protein and flax oil reduces some disease-associated pathologies in established renal disease in Han:SPRD-cy rats. The potential benefits of the antioxidant and anti-inflammatory effects on ultimate renal disease outcome in the long term remains to be determined.

Context Fever is an important sign of inflammation recognized by health care practitioners and family caregivers. However, few empirical data obtained directly from patients exist to support many of the long-standing assumptions about the symptoms of fever. Many of the literature-cited symptoms, including chills, diaphoresis, and malaise, have limited scientific bases, yet they often represent a major justification for antipyretic administration. Objectives To describe the patient experience of fever symptoms for the preliminary development of a fever assessment questionnaire. Methods Qualitative interviews were conducted with 28 inpatients, the majority (86%) with cancer diagnoses, who had a recorded temperature of ≥38°C within approximately 12 hours before the interview. A semi-structured interview guide was used to elicit patient fever experiences. Thematic analyses were conducted by three independent research team members, and the data were verified through two rounds of consensus building. Results Eleven themes emerged. The participants reported experiences of feeling cold, weakness, warmth, sweating, nonspecific bodily sensations, gastrointestinal symptoms, headaches, emotional changes, achiness, respiratory symptoms, and vivid dreams/hallucinations. Conclusion Our data not only confirm long-standing symptoms of fever but also suggest new symptoms and a level of variability and complexity not captured by the existing fever literature. Greater knowledge of patients’ fever experiences will guide more accurate assessment of symptoms associated with fever and the impact of antipyretic treatments on patient symptoms in this common condition. Results from this study are contributing to the content validity of a future instrument that will evaluate patient outcomes related to fever interventions.