bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Alcohol Intake and Serum Sex Hormones and Peptides Differs by Tamoxifen Use in Breast Cancer Survivors
Authors: Wayne Sharon , Neuhouser Marian L. , Ulrich Cornelia M. , Koprowski Carol , Wiggins Charles , Baumgartner Kathy B. , Bernstein Leslie , Baumgartner Richard N. , Gilliland Frank , McTiernan Anne , Ballard-Barbash Rachel
Published: November 2008

Objective: To measure the association between alcohol intake and 11 hormones and peptides in postmenopausal breast cancer survivors and to evaluate whether this association differs by tamoxifen use.

Methods: Self-reported alcohol intake was assessed via food frequency questionnaire on average 30 months post-breast cancer diagnosis in 490 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of alcohol intake, overall and stratified by tamoxifen use.

Results: The association between alcohol intake and serum hormone and peptide levels differed by tamoxifen use. We found statistically significant inverse associations between alcohol intake and both leptin and SHBG values but only among tamoxifen users. In women not using tamoxifen, we found a positive association between alcohol intake and DHEAS but no association in tamoxifen users.

Conclusion: Tamoxifen may modify the association between alcohol intake and serum hormones and peptides. The significant associations found for DHEAS and SHBG are in a direction considered unfavorable for breast cancer prognosis. Postmenopausal breast cancer survivors may benefit from decreasing their alcohol intake. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3224–32)
Enterolactone Is Differently Associated with Estrogen Receptor β–Negative and –Positive Breast Cancer in a Swedish Nested Case-Control Study
Authors: Sonestedt Emily , Borgquist Signe , Ericson Ulrika , Gullberg Bo , Olsson Håkan , Adlercreutz Herman , Landberg Göran , Wirfält Elisabet
Published: November 2008

Background: Differences in the estrogen receptor (ER) status of tumors may explain ambiguities in epidemiologic studies between the blood concentrations of enterolactone and breast cancer. To our knowledge, the association between enterolactone and ERβ-defined breast cancer has previously not been examined.

Methods: A nested case-control study within the Malmö Diet and Cancer cohort used 366 cases and 733 matched controls to identify the major determinants of plasma enterolactone and to examine the association between enterolactone concentration and breast cancer risk and if this association differs depending on the ERα and ERβ status of tumors. A modified diet history method assessed dietary habits. Time-resolved fluoroimmunoassay determined enterolactone concentrations and immunohistochemistry using tissue microarray determined ER status.

Results: Dietary fiber, as well as fruits and berries, and high-fiber bread showed statistically significant correlations with enterolactone (r, 0.13-0.22). Smoking and obesity were associated with lower enterolactone concentrations. Enterolactone concentrations above the median (16 nmol/L) were associated with reduced breast cancer risk when compared with those below [odds ratio, 0.75; 95% confidence interval (95% CI), 0.58-0.98]. The reduced risk was only observed for ERα [positive (+); odds ratio, 0.73; 95% CI, 0.55-0.97] and ERβ [negative (−)] tumors (odds ratio, 0.60; 95% CI, 0.42-0.84), with significantly different risks for ERβ (−) and ERβ (+) tumors (P for heterogeneity = 0.04).

Conclusions: This study supports the suggestion that enterolactone is a biomarker of a healthy lifestyle. The protective association between enterolactone and breast cancer was significantly different between ERβ (−) and ERβ (+) tumors and most evident in tumors that express ERα but not ERβ. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3241–51)
Hematopoietic Malignancies Associated with Viral and Alcoholic Hepatitis
Authors: Anderson Lesley A. , Pfeiffer Ruth , Warren Joan L. , Landgren Ola , Gadalla Shahinaz , Berndt Sonja I. , Ricker Winnie , Parsons Ruth , Wheeler William , Engels Eric A.
Published: November 2008

Hepatitis C virus (HCV) and hepatitis B virus (HBV) have been associated with hematopoietic malignancies, but data for many subtypes are limited. From the U.S. Surveillance, Epidemiology, and End Results-Medicare database, we selected 61,464 cases (≥67 years) with hematopoietic malignancies and 122,531 population-based controls, frequency-matched by gender, age, and year (1993-2002). Logistic regression was used to compare the prevalence of HCV, HBV, and alcoholic hepatitis in cases and controls, adjusted for matching factors, race, duration of Medicare coverage, and number of physician claims. HCV, HBV, and alcoholic hepatitis were reported in 195 (0.3%), 111 (0.2%), and 404 (0.7%) cases and 264 (0.2%), 242 (0.2%), and 798 (0.7%) controls, respectively. HCV was associated with increased risk of diffuse large B-cell lymphoma [odds ratio (OR) 1.52, 95% confidence interval (95% CI) 1.05-2.18], Burkitt lymphoma (OR 5.21, 95% CI 1.62-16.8), follicular lymphoma (OR 1.88, 95% CI 1.17-3.02), marginal zone lymphoma (OR 2.20, 95% CI 1.22-3.95), and acute myeloid leukemia (OR 1.54, 95% CI 1.00-2.37). In contrast, HBV was unrelated to any hematopoietic malignancies. Alcoholic hepatitis was associated with decreased risk of non–Hodgkin lymphoma overall, but increased risk of Burkitt lymphoma. In summary, HCV, but not other causes of hepatitis, was associated with the elevated risk of non–Hodgkin lymphoma and acute myeloid leukemia. HCV may induce lymphoproliferative malignancies through chronic immune stimulation. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3069–75)
Migraine in Postmenopausal Women and the Risk of Invasive Breast Cancer
Authors: Mathes Robert W. , Malone Kathleen E. , Daling Janet R. , Davis Scott , Lucas Sylvia M. , Porter Peggy L. , Li Christopher I.
Published: November 2008

Background: The frequency of migraine headache changes at various times of a woman's reproductive cycle. Menarche, menses, pregnancy, and perimenopause may carry a different migraine risk conceivably because of fluctuating estrogen levels, and in general, migraine frequency is associated with falling estrogen levels. Given the strong relationship between endogenous estrogen levels and breast cancer risk, migraine sufferers may experience a reduced risk of breast cancer.

Methods: We combined data from two population-based case-control studies to examine the relationship between migraine and risk of postmenopausal invasive breast cancer among 1,199 ductal carcinoma cases, 739 lobular carcinoma cases, and 1,474 controls 55 to 79 years of age. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).

Results: Women who reported a clinical diagnosis of migraine had reduced risks of ductal carcinoma (OR, 0.67; 95% CI, 0.54-0.82) and lobular carcinoma (OR, 0.68; 95% CI, 0.52-0.90). These associations were primarily limited to hormone receptor–positive tumors as migraine was associated with a 0.65-fold (95% CI, 0.51-0.83) reduced risk of estrogen receptor–positive (ER+)/progesterone receptor–positive (PR+) ductal carcinoma. The reductions in risk observed were seen among migraine sufferers who did and did not use prescription medications for their migraines.

Conclusions: These data suggest that a history of migraine is associated with a decreased risk of breast cancer, particularly among ER+/PR+ ductal and lobular carcinomas. Because this is the first study to address an association between migraine history and breast cancer risk, additional studies are needed to confirm this finding. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3116–22)
Childbearing Recency and Modifiers of Premenopausal Breast Cancer Risk
Authors: Peterson Neeraja B. , Huang Yifan , Newcomb Polly A. , Titus-Ernstoff Linda , Trentham-Dietz Amy , Anic Gabriella , Egan Kathleen M.
Published: November 2008

The purpose of this study was to examine the risk of premenopausal breast cancer for women in relation to childbearing recency and whether this association differs by breast-feeding history and/or the amount of weight gained during pregnancy. This analysis was based on data from a population-based case-control study composed of 1,706 incident cases of invasive breast cancer and 1,756 population controls from Wisconsin, New Hampshire, and Massachusetts. In a telephone interview conducted from 1996 to 2001, information was gathered on established breast cancer risk factors, as well as reproductive history, including amount of weight gained during the last full-term pregnancy and whether the child was breast-fed. Unconditional logistic regression was used to estimate odds ratios and Wald 95% confidence intervals for the risk of breast cancer. When compared with nulliparous women, women that had given birth within the past 5 years before breast cancer diagnosis in the cases or a comparable period in controls had a nonsignificant 35% increased risk of invasive breast cancer (odds ratio, 1.35; 95% confidence interval, 0.90-2.04), adjusting for age and known breast cancer risk factors (Ptrend = 0.14). We did not find a significant interaction with breast-feeding (Pinteraction = 0.30) or pregnancy weight gain (Pinteraction = 0.09). (Cancer Epidemiol Biomarkers Prev 2008;17(11):3284–7)
Body Size and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition
Authors: Pischon Tobias , Boeing Heiner , Weikert Steffen , Allen Naomi , Key Tim , Johnsen Nina Føns , Tjønneland Anne , Severinsen Marianne Tang , Overvad Kim , Rohrmann Sabine , Kaaks Rudolf , Trichopoulou Antonia , Zoi Gitaki , Trichopoulos Dimitrios , Pala Valeria , Palli Domenico , Tumino Rosario , Sacerdote Carlotta , Bueno-de-Mesquita H. Bas , May Anne , Manjer Jonas , Wallström Peter , Stattin Pär , Hallmans Göran , Buckland Genevieve , Larrañaga Nerea , Chirlaque María Dolores , Martínez Carmen , Redondo Cornejo María L. , Ardanaz Eva , Bingham Sheila , Khaw Kay-Tee , Rinaldi Sabina , Slimani Nadia , Jenab Mazda , Riboli Elio
Published: November 2008

Background: Body size has been hypothesized to influence the risk of prostate cancer; however, most epidemiologic studies have relied on body mass index (BMI) to assess adiposity, whereas only a few studies have examined whether body fat distribution predicts prostate cancer.

Methods: We examined the association of height, BMI, waist and hip circumference, and waist-hip ratio with prostate cancer risk among 129,502 men without cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC), using Cox regression, with age as time metric, stratifying by study center and age at recruitment, and adjusting for education, smoking status, alcohol consumption, and physical activity.

Results: During a mean follow-up of 8.5 years, 2,446 men developed prostate cancer. Waist circumference and waist-hip ratio were positively associated with risk of advanced disease. The relative risk of advanced prostate cancer was 1.06 (95% confidence interval, 1.01-1.1) per 5-cm-higher waist circumference and 1.21 (95% confidence interval, 1.04-1.39) per 0.1-unit-higher waist-hip ratio. When stratified by BMI, waist circumference and waist-hip ratio were positively related to risk of total, advanced, and high-grade prostate cancer among men with lower but not among those with higher BMI (Pinteraction for waist with BMI, 0.25, 0.02, and 0.05, respectively; Pinteraction for waist-hip ratio with BMI, 0.27, 0.22, and 0.14; respectively).

Conclusions: These data suggest that abdominal adiposity may be associated with an increased risk of advanced prostate cancer. This association may be stronger among individuals with lower BMI; however, this finding needs confirmation in future studies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3252–61)
MAMLD1 (CXorf6): A New Gene for Hypospadias
Authors: Ogata T. , Wada Y. , Fukami M.
Published: November 2008

MAMLD1 (mastermind-like domain containing 1), also known as CXorf6 (chromosome X open reading frame 6) has been shown to be a causative gene for hypospadias. This is primarily based on the identification of nonsense mutations (E124X, Q197X, and R653X) which undergo nonsense mediated mRNA decay in patients with penoscrotal hypospadias. Subsequent molecular studies have shown that (1) the mouse homolog is transiently expressed in fetal Sertoli and Leydig cells around the critical period for sex development; (2) CXorf6 protein shares homology to mastermind-like 2 (MAML2) protein that functions as a co-activator in canonical Notch signaling; (3) CXorf6 localizes to the nuclear bodies and transactivates the promoter activity of a non-canonical Notch target gene hairy/enhancer of split 3(Hes3) without demonstrable DNA binding capacity; (4) transient knockdown of CXorf6 results in significantly reduced testosterone production in murine Leydig tumor cells; and (5) CXorf6 can be regulated by steroidogenic factor 1 (SF-1). These findings suggest that the CXorf6 mutations cause hypospadias primarily because of testicular dysfunction and resultant compromised testosterone production around that period, and provide useful information for the molecular network involved in fetal testosterone production.
Long-Term Outcome of Disorders of Sex Development
Authors: Warne G.L.
Published: November 2008

The management of disorders of sex development (DSD) has been a problem area for years, partly because clinicians have started to see that not all of their patients grow up to be happy adults content with the gender assigned to them at birth, and partly because of the vigorous activities of patient advocacy organizations who have publicized their unhappiness and disagreement about current practices to the world at large and to politicians in particular. Results from a large number of long-term outcome studies have been published in the last decade and this paper attempts to give an overview of what we now know and what we still do not know about how to obtain a good outcome for our patients. Many studies have focused on a particular disorder and there have been more about congenital adrenal hyperplasia and complete androgen insensitivity (CAIS) than any of the other conditions, even though mixed gonadal dysgenesis is probably more common than CAIS. This is because researchers have wanted to know about the effects of hormones on the brain. There have been studies from a number of different countries, and cultural differences come to the fore in disorders affecting sex and gender. Very few studies have been done in Africa or East Asia so far. Long-term outcome should be studied in every treatment center, but there is a great need for study instruments to be developed that would be robust enough to use in a range of different cultural settings and languages. The studies show that while many patients fare well and are leading productive lives, gender dysphoria has been underestimated in the past and that gender counseling as well as sexual counseling should be part of the multi-disciplinary service available to patients with DSD. More emphasis is also needed on strategies to prevent the development of germ cell cancers. Urological problems in both males and females with DSD have been underestimated and deserve more attention.
Short-Term Dietary Intake of C18:1 Trans Fatty Acids Decreases the Function of Cellular Immunity in Healthy Young Men
Authors: Dlouhý P. , Kučera P. , Kraml P. , Pompachová A. , Potočková J. , Šmejkalová V. , Mokrejš P. , Jaček M. , Anděl M.
Published: November 2008

Aim: In this study, we tested the impact of short-term intake of increased amounts of C18:1 trans fatty acids (TFAs) on parameters of cellular and humoral immunity in healthy young men. Methods: Twenty-seven healthy young men were subsequently exposed to a standard diet for 7 days and an experimental TFA-enriched diet for 4 days. The mean energy content of these diets was 2,453 and 2,455 kcal/day, with 10, 35 and 55% of energy from proteins, fats and carbohydrates, respectively. Standard diet contained about 0.8 g and experimental diet 10.4 g TFAs. Plasma levels of C18:1 TFAs and immunological parameters were measured. Results: The 4-day increased consumption of C18:1 TFAs led to a significant decrease in mitogen-induced CD69 expression on CD8+ T cells as well as decreased phagocytic activity on neutrophils. After returning to the participants’ habitual diet (1 week after the end of the experimental diet), we observed a significant decrease in the mean level of circulating immune complexes. Concentrations of plasma immunoglobulins remained unchanged throughout the study. Conclusions: Acute impact of higher dietary C18:1 TFA intake on phagocytosis and cell-mediated immunity seems to be suppressive. This finding differs from results describing proinflammatory effects associated with long-term exposure to TFAs.
Folate, Vitamin B12 and Homocysteine Status in Women of Childbearing Age: Baseline Data of Folic Acid Wheat Flour Fortification in Iran
Authors: Abdollahi Z. , Elmadfa I. , Djazayeri A. , Sadeghian S. , Freisling H. , Salehi Mazandarani F. , Mohamed K.
Published: November 2008

Background: Folic acid fortification implemented mandatorily in many countries has been associated with significant increase in blood folate concentrations and reduction in the prevalence of neural tube defects. However, there are controversial findings on the probability of vitamin B12 deficiency being masked in the population after folic acid fortification. Baseline data on folate and vitamin B12 status are necessary before mandatory flour fortification is implemented. Objectives: To assess dietary intake of folate and vitamin B12 and to determine blood concentrations of folate, vitamin B12 and homocysteine in women of childbearing age as baseline data regarding folic acid fortification in Iran. Methods: A descriptive cross-sectional survey was performed with 579 healthy women as a representative sample of the Golestan province. Fasting blood samples were taken and dietary (24-hour recall), health and sociodemographic data were collected with an interview. Serum concentrations of folate and vitamin B12 were measured with radioimmunoassay, and plasma homocysteine concentrations were assessed by high-performance liquid chromatography with fluorescence detection. Results: Mean serum concentrations of folate and vitamin B12 were 13.6 nmol/l (95% CI 12.8–14.4) and 194.4 pmol/l (95% CI 183.8–205.0), respectively. Inadequate serum folate levels were present in 14.3% of the women and 22.7% had serum vitamin B12 levels below normal. Mean plasma homocysteine concentration was 12.6 µmol/l (95% CI 12.1–13.2) and hyperhomocysteinemia was observed in 38.3% of the women. Mean daily intake of folate and vitamin B12 was 198.3 µg (95% CI 185.4–211.3) and 2.6 µg (95% CI 1.9–3.2), respectively. Folate intake from food was positively correlated with serum folate concentrations (r = 0.084, p < 0.05) and inversely correlated with plasma homocysteine concentrations (r = –0.115, p < 0.01). Conclusions: An insufficient vitamin B12 as well as folate status is present in Iranian women of childbearing age. The final evaluation will be carried out 18 months after flour fortification and the results will be compared with baseline data obtained from the present study in order to show the efficacy and safety of folic acid fortification in Iran.
Lack of Effect of Potassium on Fluid Absorption in Isolated, Perfused Snake Proximal Renal Tubules
Authors: Dantzler William H. , Bentley Sherril K.
Published: November 2008

Effects of alterations in potassium concentrations on net fluid absorption (Jv) by isolated, perfused snake (Thamnophis spp.) proximal renal tubules were studied. With standard (3 mmol/l potassium, 150 mmol/l sodium) Ringer’s solution in perfusate and bath, Jv was about 1.3 nl min-1 mm-1. Replacing potassium with sodium in perfusate or in both perfusate and bath had no significant effect on Jv. Increasing potassium concentration to 100 mmol/l in place of sodium in perfusate or in both perfusate and bath also had no effect on Jv. Findings that potassium is not critical for maintaining Jv are also consistent with previous findings that sodium is not necessary for maintaining Jv.
Interlobular Arterial Pressure in the Rat Kidney
Authors: Tønder Heyeraas , Aukland K.
Published: November 2008

Pressure in the interlobular arteries (Pila) in the rat kidney was measured by micropuncture after acute ablation of a slice of the renal cortex. The interlobular arteries (ILA) were identified by intra-aortic injection of 25 µm microspheres, which embolized in the ILA mainly in the outer third of the cortex. Measurements proximal to the arrested spheres showed an average pressure drop of 32mmHg between the aorta and the punctured ILA, locating about 50% of the preglomerular resistance proximal to the afferent arteriole. Spontaneous, interindividual differences in mean arterial pressure in the range of 91-125mmHg were not associated with a consistent change in Pila, while lower aortic pressures seemed to be associated with almost proportional lowering of Pila-
RNA and DNA Contents of Kidneys from Rats with Unilateral Ureteral Ligation
Authors: Murray Robert D. , Malvin Richard L. , Northrup Thomas E.
Published: November 2008

Renal RNA and DNA contents, as well as estimates of renal plasma flow and glomerular filtration rate, were studied in albino Sprague-Dawley rats subjected to either unilateral nephrectomy and/or unilateral ureteral ligation. RNA and DNA contents of ligated kidneys were markedly higher than those of the contralateral, unligated kidney 24 and 48 h post ligation. These increases in RNA and DNA content of the ligated kidney occurred in the presence of relative decreases inreal plasma flow and glomerular filtration rate in the ligated kidney. Renal RNA and DNA contents were also increased in the remaining kidney following unilateral nephrectomy. The effect of ureteral ligation and unilateral nephrectomy on renal RNA content was found to be additive. These results are inconsistent with theories stating that changes in renal RNA and DNA content are the result of increased renal plasma flow and glomerular filtration rate. The data support a role for a circulating factor which either stimulates renal RNA and DNA accumulation from the lumental aspect of tubular cells or inhibits renal RNA and DNA accumulation from the peritubular aspect of these cells.
Effect of Combined PGE1, Intra-arterial Infusion, and Reduced Renal Perfusion Pressure on Renin Release
Authors: Hockel Gregory M. , Selkurt Ewald E. , Weinberger Myron W.
Published: November 2008

Continued infusion of PGE1 into the canine renal artery results in an initial increase in renin release (RR), which progressively declines to control levels and less. Subsequent partial clamping of the renal artery with continued infusion of PGE1 causes a second marked surge of RR. These results suggest involvement of two types of renin release mechanisms, a PGE sensitive one, probably involving the electrolyte sensor of the macula densa, and a baroreceptor sensitive mechanism, stimulated by renal arterial clamping. It is suggested that it is the former mechanism, after initial stimulation, which appears to be progressively inhibited by the continued infusion of PGE1.
Influence of Age, Sex, and Dietary Salt Intake on Rat Kidney Brush Border Enzymes
Authors: Kirschbaum Barry B.
Published: November 2008

The kidney brush border membrane contains several glycoprotein hydrolytic enzymes the functions of which are currently in doubt. We have assessed the importance of age, sex, and salt intake as determinants of the activity of 5 brush border enzymes. No effect of salt loading or depletion could be appreciated. Enzyme levels corrected for age were uniformly higher in males than females except for alkaline phosphatase. Age-related changes in activities were observed to follow a nonuniform pattern with the most striking alterations affecting alkaline phosphatase and maltase in female rats. Age-associated reductions in renal function do not entirely account for reduced enzyme levels.
Effect of Intravascular Volume Expansion on Renal Hemodynamics in the Nonhuman Primate
Authors: Peterson Thomas V. , Gilmore Joseph P. , Zucker Irving H.
Published: November 2008

Experiments were performed in anesthetized Macaca fascicularis monkeys to examine the renal hemodynamic responses of these animals to a 15% blood volume expansion using isooncotic dextran in isotonic saline. 20 min following the onset of volume expansion, effective renal plasma flow had increased 80%, glomerular filtration rate was unchanged from control and filtration fraction had decreased 34%. At 50 min, effective renal plasma flow was still increased 74%, glomerular filtration rate had increased 39% and filtration fraction remained decreased 24%. These disproportionate changes in renal plasma flow and glomerular filtration rate are similar to the reported effects in man. Furthermore, they would suggest that glomerular filtration in the primate may not be highly plasma flow dependent under these conditions.
Effect of Imidazole on the Dynamics of Glomerular Ultrafiltration in the Rat
Authors: Baylis Christine
Published: November 2008

Measurements were made of the determinants of single nephron glomerular filtration rate and whole-kidney urinary excretion rates in Munich-Wistar rats which possess surface glomeruli accessible to micropuncture. During administration of imidazole (i.e., inhibition of thromboxane A2 synthesis) no change was observed in the single nephron glomerular filtration rate or in the glomerular plasma flow rate although the glomerular capillary hydrostatic pressure rose and the glomerular capillary ultrafiltration coefficient fell significantly. Urinary sodium excretion and urine volume increased significantly with imidazole. The response of all variables to imidazole was similar in rats previously fed on a normal sodium diet and in those previously maintained on high sodium intake.
Alterations in Renin Release by PGE2 and Acetylcholine in Indomethacin-Treated Dogs
Authors: Nascimento Luiz , Figueroa José , Fiallo Alfredo , Martinez Ramonita , Martinez-Maldonado Manuel
Published: November 2008

We evaluated the effect of intrarenal vasodilatation on renin release in the indomethacin (2 mg/kg) treated pentobarbital anesthetized dog. Pretreatment with indomethacin resulted in a significant decrease in renal plasma flow (RPF) without change in glomerular filtration rate (GFR). Intrarenal infusion of prostaglandin E2 (PGE2, 2 µg/min) and acetylcholine (ACh, 40 µg/min) completely restored RPF in these dogs. Following PGE2 administration a significant increase in absolute sodium excretion (UNaV), renal vein renin activity (RVRA), and renin secretory rate (RSR) were observed. Despite similar effects on RPF and UNaV, acetylcholine did not alter renin release as measured by plasma renin activity (PRA), RVRA or RSR. These results show that vasodilatation alone is not the mechanism by which exogenous PGE2 increased renin release during cyclo-oxygenase inhibition.
Effect of Hypocalcemia on Divalent Cation-Activated ATPase and Ca2+ Uptake in Microsomes of Rat Kidney Cortex
Authors: Dan Takashi , Gemba Munekazu
Published: November 2008

Effects of hypocalcemia on Ca2+ metabolism of microsomes from rat kidney cortex were studied. Microsomal activities of Ca2+-ATPase, Mg2+-ATPase and (Na++K+)-ATPase increased 30–33 days after Ca2+ restriction or low Ca2+· vitamin D depletion, but alkaline phosphatase activity decreased. Calcium repletion in diet and injection of lα-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol were partially successful in returning Ca2+-ATPase and Mg2+-ATPase activity, but not (Na++K+)-ATPase and alkaline phosphatase activity, to normal. Correlations between serum Ca2+ level and both ATPase activities were significant. ATP-dependent Ca2+ uptake of microsomes was not affected by hypocalcemia and vitamin D metabolites.
Reduced Susceptibility of Nonenzymatically Glucosylated Glomerular Basement Membrane to Proteases
Authors: Lubec Gert , Pollak Arnold
Published: November 2008

Glomerular basement membrane (GBM) preparations were enzymatically glucosylated and applied to proteolytic degradation by several enzymes. The split products were then characterized and quantitatively estimated by high pressure liquid chromatography. For this purpose, GBMs were isolated by a sieving and sonication method, incubated with glucose and digested with the proteases trypsin, chymotrypsin, papain, pepsin and a lysosomal preparation. Comparison of the concentrations of split products obtained by proteolytic degradation of normal and nonenzymatically glucosylated membranes showed a remarkable reduced susceptibility of the nonenzymatically glucosylated membranes, possibly due to steric hindrance or altered electrical charge of the glucosylated membrane proteins. This could be interpreted as an additional factor for accumulation of basement membrane material in the diabetic state, that not only increased basement membrane synthesis may occur but also reduced catabolism could possibly contribute to the diabetic changes.
Isolation of Human Glomerular Basement Membrane Antigens by Affinity Chromatography Utilising Goodpasture’s Kidney Antibody Eluates
Authors: Hunt J.S. , Macdonald P.R. , McGiven A.R.
Published: November 2008

The soluble material produced from a 96-hour digest of sonicated human glomerular basement membranes with purified collagenase was shown to contain at least 12 components by sodium dodecyl sulphate-polyacrylamide gel electrophoresis with molecular weights ranging from 20×103 to greater than 200 ×103 daltons. Five of these components produced antigenic peaks after two-dimensional immunoelectrophoresis into agar plates containing rabbit antiserum to the solubilised glomerular basement membrane. Two groups of antigenic components were demonstrated in these gels by two-dimensional immunoelectrophoresis autoradiographic techniques utilising 125I-labelled collagenase-digested human glomerular basement membranes reacted with antibodies eluted at acid pH from the kidney of the Goodpasture’s patient. This acid eluate was shown to contain contaminants of α1-antitrypsin and albumin co-eluting with the antibodies bound to the glomerular basement membrane. After removal of these contaminants, the antibodies were linked to cyanogen bromide-activated Sepharose and used to affinity purify four antigenic fractions from the collagenase-digested glomerular basement membrane. These fractions were eluted by 0.2 Mglycine pH 2.8 and with 0.5 Mammonium thiocyanate and had molecular weights of 22–25,43–45,65–70 and 205 ×103 daltons. The smaller molecular weight components were shown to be common to both included and excluded fractions obtained by Ultragel AcA 44 chromatography of the digested material in 10 mM phosphate pH 8. This suggests that the larger molecular weight component would be an aggregate of a smaller component. Preliminary carbohydrate and amino acid analyses indicated that the different elution procedures elicited antigens with different chemical characteristics.
Effect of Anaesthesia and Surgery on Urine Flow and Electrolyte Excretion in Different Rat Strains
Authors: Thomsen Klaus , Olesen Ole Vendelin
Published: November 2008

The suitability of some commonly used experimental procedures for studying the effect of chronic alterations of sodium excretion on lithium clearance was examined in Wistar rats and Sprague-Dawley rats. The animals were maintained on diets with standardized sodium content for 10 days before the investigation. Urine flow and clearance values were measured in (1) awake unoperated rats, (2) awake catheterized rats and (3) anaesthetized rats of both strains. Awake unoperated and awake catheterized Wistar rats showed almost identical urine flows and clearances of sodium and lithium. Amytal anaesthetized Wistar rats showed significantly depressed urine flows and clearances of sodium, lithium and inulin as compared with awake rats. Awake unoperated and awake catheterized Sprague-Dawley rats showed almost identical clearance values but the urine flow rates were increased about fivefold in the awake catheterized Sprague-Dawley rats. Amytal anaesthetized catheterized Sprague-Dawley rats showed unchanged urine flows and clearance values as compared with awake rats. Inactin anaesthesia reduced the urine flows and clearance values in both Wistar rats and Sprague-Dawley rats. It is concluded that anaesthesia and surgery affect the kidney function to different degrees in different rat strains, amytal anaesthetized Sprague-Dawley rats being the least influenced. If exposure of the kidney is unnecessary, awake catheterized Wistar rats offer a suitable experimental procedure for determination of urine flow and urinary clearances of sodium and lithium.
The Renal Clearance of Albumin following Intravenous Loading of Homologous Albumin in Conscious Rats
Authors: Hackbarth H. , Alt J.M. , Gärtner K. , Sindermann H.
Published: November 2008

Tubular reabsorption of albumin was studied in conscious rats by measuring the renal excretion at various plasma concentrations. The plasma albumin concentration was raised by loading the animals with homologous serum albumin. By using this procedure an average plasma concentration of 54g/l could be reached, which is about twice the physiological plasma albumin concentration in untreated rats. Throughout the experiments the glomerular filtration rate was determined by the total plasma slope clearance of 51Cr-EDTA. Following the albumin load, the 51Cr-EDTA clearance remained at 54.8 +12.2ml/min/m2 body surface. By correlating renal albumin excretion and plasma albumin concentration, the sieving coefficient of albumin, φ, of 2.35 ×10-4, the renal albumin threshold of 38 ± 5g/l, and the maximal tubular transport rate of albumin of 9.6 ± 2.6µg/min/g kidney weight could be calculated (mean ± SD). There were some variations among the animals, resulting in a fairly large standard deviation. However, these values are in agreement with recent micropuncture data.
Head-Up Tilt in the Nonhuman Primate
Authors: Peterson Thomas V. , Chase Nancy L. , Gray Debbi K.
Published: November 2008

Experiments were performed to determine the role of the renal nerves in mediating the antinatriuresis of head-up tilt in the nonhuman primate. Male Macaca fascicularis monkeys underwent chronic bilateral renal denervation or sham surgery and were allowed a 1- to 2-week recovery period. After that time, each animal was anesthetized with sodium pentobarbital and subjected to 40 min of 35° head-up tilt. Renal perfusion pressure was maintained constant throughout the experiment. Tilt caused significant decreases in urine flow, sodium excretion and osmolar clearance and increases in urine osmolality in both groups. Creatinine and para-aminohippurate clearances decreased in the sham-operated animals but were unchanged in the denervated animals. Although the pattern of the renal excretory responses showed some group differences in that a significant antidiuresis and antinatriuresis occurred after 10 min of tilt in the sham-operated group but not until 20 min in the denervated group, the magnitudes of these excretory responses were similar in both groups throughout the entire tilt procedure. These results suggest that, in this species, the renal nerves are not necessary for eliciting the overall antinatriuretic response to orthostasis but may have some minor involvement in the onset of the response.
Effects of Captopril on the Renal Hemodynamics during Aprotinin Infusion in Anesthetized Dogs
Authors: Mizumura Yasuji , Matsumoto Michio , Nishino Akira , Takata Masanobu , Iida Hiroyuki , Sugimoto Tsuneaki
Published: November 2008

The effect of captopril (SQ 14, 225) on the renal hemodynamics, cortical plasma flow (CPF) and noncortical plasma flow (NCPF), was studied in sodium-replete anesthetized dogs during aprotinin infusion. Mean blood pressure (MBP) increased by aprotinin (p < 0.05) and decreased by captopril (p < 0.02). Renal vascular resistance (RVR) tended to increase by aprotinin and decreased from 1.29 to 0.86 mm Hg/ml/h (74.7%) by captopril (p < 0.05). Renal vein renin activity (RRA) inclined to decrease by aprotinin and increased from 17.8 to 47.2 ng/ml/h (278.2%) by captopril (p < 0.05). Although the administration of captopril alone did not alter the renal hemodynamics despite the reduction of MBP, captopril made a recovery of renal plasma flow (RPF), CPF and NCPF which had decreased by aprotinin. Especially, CPF showed a significant recovery from 45.4 to 55.6 ml/min (123.6%) by captopril (p < 0.02). These results indicate that the inhibition of endogenous angiotensin made a preferential increase in CPF and suggest that the renin-angiotensin system plays a major role in the effect of captopril of the renal hemodynamic changes.
Stereo-Specificity of Diuretic Receptors in the Nephron: A Study of the Enantiomers of Indacrinone (MK-196) in Man
Authors: Brooks B.A. , Lant A.F. , McNabb W.R. , Noormohamed F.H.
Published: November 2008

Urinary clearance techniques have been employed to compare the renal sites of action of three phenoxyacetic acid diuretics in man: ethacrynic (etacrynic) acid and the two enantiomers of indacrinone (MK-196). The effects of these compounds on fractional free-water clearance and reabsorption during maximal hydration and hydropenia, respectively, indicate that whilst ethacrynic acid and (-)-indacrinone have their natriuretic site of action in the medullary portion of the thick ascending limb of Henle’s Loop, the (+)-enantiomer of indacrinone acts in the ‘cortical diluting segment’ or early distal tubule. The natriuretic potencies of all three agents are different as is their effect on the renal handling of uric acid. Ethacrynic acid produces minor urate retention whilst both enantiomers of indacrinone produce uricosuria and hypouricaemia. The apparent difference in the renal sites of action of the enantiomers of indacrinone is discussed in relation to our current knowledge of stereo-selectivity in other pharmacological systems.
Effect of Free Fatty Acids on Renal Metabolism of Very Low Density Lipoprotein Triglyceride
Authors: Trimble Mary Ellen
Published: November 2008

Metabolism of very low density lipoprotein-triglyceride (VLDL-TG) was studied in the isolated perfused rat kidney (IPRK). Recirculating perfusate consisted of KrebsHenseleit bicarbonate buffer containing 6% defatted albumin and VLDL-TG which has been labelled in vitro with 14C-tripalmitin. Results show that the IPRK catabolizes VLDL-TG. Renal removal of VLDL-TG from perfusate was impaired in the presence of 1.0 mM palmitate. A lower palmitate concentration, 0.4 mM, was without effect. It is concluded that high concentrations of circulating free fatty acids impair renal metabolism of fatty acids derived from VLDL-TG.
Production and Excretion of Dopamine by the Isolated Perfused Rat Kidney
Authors: Adam William R. , Adams Beverlie A.
Published: November 2008

Renal catecholamine concentrations and urinary dopamine excretion from the isolated perfused kidney were measured in intact and peripherally sympathectomized rats. Urinary dopamine excretion was not diminished by sympathectomy, was increased by l-dopa (but not tyrosine or dopamine 4-O-sulphate) in the perfusate and was virtually abolished by prior treatment with the dopa decarboxylase inhibitor, carbidopa. These results confirm the importance of renal extraneuronal dopamine production, from circulating l-dopa, as a contributor to urinary dopamine excretion.
Effects of PGE2 Infusion on Renal Function in Normal Man before and after Angiotensin II Inhibition by Captopril
Authors: Usberti Mario , Cianciaruso Bruno , Di Minno Giovanni , Auciello Antonio , Ardillo Gianfranco , Bonanno Domenico , Conte Giuseppe , Andreucci Vittori E
Published: November 2008

Increasing doses of prostaglandin E2 (PGE2) (5, 10, 20, 40, 60 ng/kg/min) were infused in 7 normal volunteers before and after angiotensin II synthesis inhibition by captopril (100 mg by mouth). PGE2 infusion alone did not alter blood pressure, while it increased the urinary excretion of both epinephrine and norepinephrine, enhanced p aminohyppuric clearance (CPAH), inulin clearance (CIn), sodium and water excretion and decreased urinary osmolality. No changes of CIn CPAH and catecholamines were observed after captopril alone, whilst there was a significant increase in urine output and sodium excretion and a decrease in urinary osmolality. In the presence of captopril, the infusion of PGE2 caused a significant fall in blood pressure and CIn, enhanced epinephrine excretion and sodium excretion, while it did not significantly reduce CPAH· Our findings suggest that an intact renin-angiotensin system is necessary to maintain GFR during PGE2 infusion.
Enhancement of Angiotensin-Converting Enzyme Activity in the Inner Cortex of Rat Kidney by Captopril
Authors: Song Gyeong-Bu , Tominaga Munechika , Kanayama Yoshiharu , Ikemoto Fumihiko , Yamamoto Kenjiro
Published: November 2008

The rat kidney was separated into the outer cortex, inner cortex, outer medulla and inner medulla or papilla, and the distribution of angiotensin-converting enzyme (ACE) in response to consecutive administrations of captopril was studied. In normal animals, the ACE activity in the inner cortex and outer medulla was about 10 and 3 times higher than in the outer cortex, respectively, and the activity in the inner medulla was much the same as that in the outer cortex. Captopril was given in doses of 30 and 100 mg/kg/day for 7 days, and the renal ACE activity on the 8th day was examined. Since it was assumed that the ACE activity might be lower than the full activity when the tissue contained captopril, diamide, a sulfhydryl oxidant, was used to eliminate the effect of any captopril remaining in the tissue extracts. However, this compound at concentrations over 1 mM enhanced the activity of ACE itself to about twice the value when assayed without diamide. Thus, oxidation with sufficient concentrations of diamide resulted in an enhancement of a maximal activity of ACE. When all samples were pretreated with 10 mM diamide and the ACE activity determined, captopril caused a dose-related increase in the ACE activity, but only in the inner cortex. We conclude that ACE locates predominantly in the inner cortex of the rat kidney and it is this area which has an altered ACE activity in response to captopril.
Quantitative Morphologic Changes of Nephron Structures and Urinary Enzyme Activity Pattern in Sodium-Maleate-Induced Renal Injury
Authors: Pfaller Walter , Joannidis Michael , Gstraunthaler Gerhard , Kotanko Peter
Published: November 2008

The morphologic changes in sodium-maleate-induced acute renal injury in the rat were quantified by a stereologic analysis. The major changes were confined to an increase in endocytic vacuoles and a decrease in mitochondrial inner membrane surface area. These results were found to be linked to significantly increased urinary activities of the cytosolic enzymes fructose-1 6-bisphosphatase (FBP) and lactate dehydrogenase, the lysosomal enzyme N-acetyl-β-glucosaminidase (NAG) and the NAD-dependent mitochondrial isocitrate dehydrogenase (ICDH). The highest increase was found for NAG, followed by FBP and ICDH.
31P Nuclear Magnetic Resonance and Saturation Transfer Studies of the Isolated Perfused Rat Kidney
Authors: Dowd T. , Barac-Nieto M. , Gupta R.K. , Spitzer A.
Published: November 2008

Previous studies using 31P nuclear magnetic resonance (NMR) saturation transfer techniques to quantitate the energy metabolism of the kidney have often resulted in estimates of adenosine triphosphate (ATP) turnover which are much lower than those predicted from the renal oxygen consumption and reasonable values of the P/O ratio. We measured the ATP turnover in isolated perfused kidneys of rats, using 31P NMR saturation transfer and a new procedure for quantitation of the intracellular Pi concentration. The estimated turnover rates of ATP were higher than previously reported. The P/O ratios calculated on the basis of these rates of ATP turnover and rates of renal oxygen consumption reported in the literature were within the range of theoretically possible values. Thus, 31P NMR saturation transfer can be used to quantitate the ATP turnover in the isolated perfused rat kidney.
Methylamines and Polyols in Kidney, Urinary Bladder, Urine, Liver, Brain, and Plasma
Authors: Gullans Steven R. , Heilig Charles W. , Stromski Michael E. , Blumenfeld Jon D.
Published: November 2008

Methylamines and polyols are known to behave as organic osmolytes in the adaptation of many cells to hyperosmolar conditions. Using 1H nuclear magnetic resonance spectroscopy to analyze perchloric acid extracts we have examined several tissues in the rat for the presence of these compounds. Methylamines such as glycerophosphorylcholine, choline and betaine were observed in the renal inner medulla, urinary bladder, urine, liver, brain, and plasma. Myo-inositol was relatively abundant in the renal inner medulla and brain whereas sorbitol was detected only in the inner medulla. A variety of unidentified compounds was also detected in each tissue. Although these methylamines and polyols are known to respond to osmotic changes in the renal inner medulla, their responses in other tissues remain to be investigated.
Renal Uptake and Degradation of Trapped-Label Insulin
Authors: Hysing Jan , Tolleshaug Helge , Kindberg Grete M.
Published: November 2008

In order to study the kinetics of insulin degradation in the kidneys and liver, insulin was labelled by a trapped-label procedure and injected into rats. In contrast to conventional 125I-insulin, the trapped-label preparation allows quantitative measurements of the extent of degradation in vivo because the final degradation products do not leave the cells. One hour after injection, the amount of radioactivity in the kidneys from a trace dose of trapped-label insulin was 10 times higher than that from conventionally labelled insulin; over 80% of the increase was due to low molecular weight degradation products which were retained in the kidneys. The amount of acid-precipitable radioactivity in the blood was the same for both labelled preparations, indicating that their rates of clearance were similar. In the kidney, we detected no degradation products of molecular weight intermediate between intact insulin and the end products of proteolysis. After 2h, 33% of the injected dose remained in the kidneys and only 13% in the liver. Over 80% of the renal radioactivity was sedimentable in an isotonic density gradient, indicating that intact insulin, as well as degradation products in the cells, were enclosed within membrane-bound vesicles.